How did you get interested in Medicinal Chemistry?

As I wrote in my very recently published scientific autobiography in the Serie Lives in Chemistry (https://l-i-c.org/horst-kessler.html), I was trained as Organic Chemist (synthesis of small ring compounds) at the University of Tübingen under the guidance of Eugen Müller in my Ph.D. After my thesis I studied rapid intramolecular rearrangements by NMR-spectroscopy. After habilitation I obtained a call to the Johann-Wolfgang-Goethe-University in Frankfurt as Full-Professor at the age of 31 years.

There I became interested in peptide synthesis and conformational studies by NMR. After 18 years in Frankfurt I moved as professor of Organic Chemistry and Biochemistry to the Technical University Munich (TUM). We developed a number of novel multidimensional NMR techniques in combination with molecular dynamics to achieve reliable pictures of peptide conformations. This knowledge was used to design biological active conformationally restrained peptides with super-activities and receptor subtype selectivity. 

My interest shifted to application of those peptides as drugs of for molecular imaging (after radiolabeling for SPECT and PET). Finally my main interest was in the design of orally active peptides (via conformational restraints and multiple N-methylation.

Where are you currently working and what is your current position?

After my official retirement in 2008, I became a member of the IAS and member of the Senior Excellence Faculty and was granted to do lab work until 2019. 

How did you get interested in Computational Chemistry? 

I obtained a Bachelor's degree in Pharmacy in 2018 from the German University in Cairo, Egypt. Despite coming from a family with no scientific background, I was driven by my passion for science and this is why I decided to move to France to pursue a career in research. During my final year of pharmacy, I was exposed to the world of computational chemistry and in silico drug discovery. This field fascinated me because of its ability to use simulation and computer-based tools for the drug discovery process. This is why I was enrolled in a master program where I gained extensive knowledge in molecular modelling then pursued a PhD in the same field.  

Where and when did you obtain your PhD diploma?

Currently in my third year of PhD at the University Paris Cité and I will obtain my PhD by the end of 2024.

What was the topic of your PhD project?

Nanobodies targeting mGlu receptors as innovative agents for schizophrenia.

What are your current research interests?

Using in silico drug design and molecular modelling for the development of nanobodies to target metabotropic glutamate receptors. Including the protein structure prediction, epitope identification and nanbody re-design or re-epitoping. 

How would you explain what your research area is to non-scientists?

The main idea is to develop nanobodies (which are 10 times smaller than antibodies) to target certain receptors involved in schizophrenia. Using an analogy, one can think of nanobodies as Lego pieces that are already designed to bind to a specific target. The first step is to understand where the nanobody binds and how it interacts with the target receptor, and then try to redesign the nanobody so that it can bind to a different receptor for therapeutic purposes.

What do you like best about your work?

The field of my work is highly evolving, so every day presents a chance to learn something new and apply it to my research.

What kind of tasks does your work involve?

Mostly working on computers, I am focused on modelling the structures of nanobodies and receptors to understand how they bind together. I also conduct simulations to observe their movement and behaviour on a nanosecond scale.

What kind of skills does your work require?

A strong background in chemistry and biology is required to understand the principles of molecular interactions. As well as an expertise in programming and computational methods is crucial for designing and running simulations. But since it is an interdisciplinary field, I strongly believe that anyone who has the will to learn can acquire the necessary skills and knowledge to excel in this domain. 

What do you consider your greatest achievement in your scientific career? 

Still early since I am at the beginning of my career but the day the biology confirmed a hypothesis I suggested using molecular modelling was one of the best moments.

How did you get interested in Chemical Biology?

Early on in my chemistry studies I became intrigued by the synthetic potential of enzymes and our budding capability to engineer them into even more useful catalysts.

Where and when did you obtain your PhD diploma?

I obtained my PhD diploma from ETH Zurich in 2011 with Professor Donald Hilvert. I worked on the “Directed Evolution of Artificial Enzymes”: Using an in silico designed enzyme as a starting point, we evolved the new-to-nature biocatalyst to exhibit “natural” enzyme-like activity.

After my PhD, I started to work in industry (Firmenich SA) and led a laboratory for biocatalytic transformations to obtain fragrance and flavour compounds.

How did you get interested in Medicinal Chemistry?

I was first attracted by the beauty and complexity of natural product total synthesis and was trained therefore as an expert in asymmetric synthesis. My PhD was however already focused on the development of HIV inhibitors and this Medchem training was reinforced during my industrial postdoc position at Novartis working on selectins and integrins. I got my PhD in asymmetric synthesis from the university of Strasbourg in 1995. Strasbourg has always been a centre of excellence in chemistry in Europe and I definitely learnt a lot.

Where did you have your postdoc position?

I did my postdoctoral study in Central Research at Ciba-Geigy. This experience was extended for one year in the transplantation department at Novartis following Sandoz and Ciba-Geigy merger. This gave me the opportunity to work on 2 different sites in Basel Switzerland and East Hanover US and to discover different cultures of working. 

Where are you currently working and what is your current position?

I am Chief Scientific Officer at Edelris, a CRO company I have co-founded in 2005.

What are your current research interests?

My strong interest remains in the identification of molecular tools to explore new targets related to diseases that could potentially lead to the identification of a drug. We explore new molecular frameworks based on innovative chemistry and have developed a specific expertise in affinity selection-mass spectrometry to assess the activity of these compounds against challenging targets.

My work requires performing scientific intelligence, developing R&D projects and ensuring financing and monitoring. I like to stay in close contact with the team to stimulate their creativity and help them as much as I can in solving problems. Ensuring the worldwide visibility of the company is also a priority. Networking and communication are among the tasks affiliated with my responsibilities. The most exciting is to foster creativity and work with a bunch of multidisciplinary experts to achieve a specific goal. I never got bored of that after 30 years in this field.

How many PhD students and postdocs do you currently supervise?

I have the responsibility of 1 PhD student in the frame of an MSCA-Innovative Training Network collaboration aiming at the identification of inhibitors of helicases. We have applied for another public funding to host 1 PhD student working on RNA modulation.

As supervisor, I always tried to motivate my collaborators to give the best of themselves, to provide them with a stimulating environment and act as a facilitator instead of a controller.

What do you consider your greatest achievement in your scientific career? 

I have directly contributed to the clinical development of 4 drug candidates and have co-founded Edelris, a Drug Discovery CRO company that has been in activity now for 18 years. We have overall recruited and trained over 100 PhD since the inception and this is probably my best reward.

Which of your papers are you most proud of and why?

As a young process chemist, I have published in 2001 an article in Org. Process R&D describing the optimization and scale-up of a novel process for 2-aminoindan hydrochloride production. At Novartis, the scale-up of a drug candidate was compromised due to a shortage of the main starting material 2-aminoindan. Under the guidance of my mentor Kapa Prasad, I proposed to prepare this material by an unprecedented route which turned out to be successful and allowed the due delivery of one first batch of the drug candidate. 

What are the features of a successful PhD student or postdoc?

A good researcher should be thoughtful, curious and persevering. As stated by Pasteur “Fortune favours the prepared mind”!

What would you like to ask from other medicinal chemists?

Although we are working in a competitive field, we should not forget that our ultimate goal is to provide new therapies for patients. I will advocate sharing failures and successes through collaborative networks, publications and conferences.    

Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?

Certainly. I remember one particular situation where a project was heavily relying on the synthesis I had developed of a complex natural product. This project was at one time transferred to another department and I was eventually not cited as a co-author on the patent application. Rewarding individuals in a multidisciplinary process implying a long list of contributors is not always easy.  

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

During my first years at the university, we used to dry glassware with an open-flame Bunsen burner. I accidentally set fire to a Dewar vessel containing acetone. The fire was fortunately stopped very quickly with the intervention of a more experienced supervisor.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

I like to advertise for young medicinal chemists the EFMC webinar “Best practice in medicinal chemistry”. The Suisse course on Medicinal Chemistry organized for many years by my former supervisor Beat Ernst is also a fantastic training for young medicinal chemists. The Kerns “Drug-like properties: concepts, structure design and methods” has been for many years my bible when working on improving ADME/tox properties of compounds. Among the blogs, Derek Lowe’s commentary on drug discovery “In the Pipeline” is certainly a must-read.

Which scientist do you admire the most and why?

Barry Sharpless 2 times Nobel prize in chemistry. His work opened whole new scientific frontiers that have had a major impact on the fields of chemistry, biology and medicine. 

Which field of medicinal chemistry do you consider the most promising for the future?

The field of PROTACs and molecular glues has reactivated a strong interest in small-molecule drug discovery. This is very exciting for our community which has suffered for the last 20 years from the competition with New Biological Entities (NBE).  

What would you expect to be the next major breakthrough in medicinal chemistry?

When compared to disciplines like engineering, medicinal chemistry remains very experimental. Computational chemistry has not delivered yet the results expected to provide better predictions and accelerate the DMTA cycle (Design-Make-Test-Analyse). I expect a real breakthrough of artificial intelligence in the years coming.   

How did you get interested in Medicinal Chemistry?

I was always interested in nature and science from an early age. I took Biology, Chemistry and English at A-level (I never liked Maths of Physics) and did an undergraduate degree in Chemistry with Biological Chemistry, with a PhD project on Synthesis of Anthracyclinones.

Where are you currently working and what is your current position?

I have been Head of Medicinal Chemistry for a French biotech called Antabio for around 12 years. This is no longer a full time position and now I also manage medicinal chemistry projects for an Indian CRO called o2h. Previously I worked as a medicinal chemist at GSK and heritage companies, but since leaving around 15 years ago I mainly work from home (near London), working on site for meetings as and when.

What are your current research interests?

I work in antibacterials, Cystic Fibrosis, oncology, Parkinsons Disease plus some novel antiaging projects.

How would you explain what your research area is to non-scientists?

I do drug design for new medicines (and no, I don’t make pills).

What do you like best about your work?

I love having an idea about how to change a molecule to affect some biological activity or property, and see it work out. Ii doesn’t happen that often, most good ideas fail.

What kind of skills does your work require?

Medicinal chemistry skill and synthetic chemistry skills, organisational, communication and people skills plus a love of science and the desire to learn more every day. Plus the determination to carry on when things look difficult.

What do you consider your greatest achievement in your scientific career?

From my GSK days we have a drug which is being launched this year and from my Antabio days we have a drug going into Phase 1 this year. I am most proud of the J Med Chem paper describing the Antabio Phase 1 drug, because we achieved an asset in a crowded area with 6 chemists in 6 months.

What are the features of a successful PhD student or postdoc?

You have to enjoy doing research. Don’t be afraid to change things if your work is going badly – success is your responsibility as much as your supervisor’s. Read the literature. Every day.

What advice would you give to someone who wants to know more about your field?

Depends on what level they are at. If a synthetic chemistry PhD student, try reading med chem journals like ACS Med Chem Lett.

Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?

Absolutely. From poor organisational culture, through poor managers, to unfair funding body decisions. Life is unfair, but don’t worry, no situation is permanent. Try to take control.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

During my PhD I had a friend who got a job selling life insurance, so I said I would buy a policy from him and he could meet me at the lab. As he walked in, I dropped a Winchester of conc. HCl which smashed and the HCl began to react with a metal container next to it containing sodium. I screamed “Get out” to him while I sorted the problem out. (He still sold me the life insurance, though.)

Which scientist do you admire the most and why?

It has to be Watson and Crick. Changed the world.

What would you expect to be the next major breakthrough in medicinal chemistry?

I am close to the end of my career now, so I will leave that question for the next generation, but I don’t think it will be due to AI.

How did you get interested in Medicinal Chemistry?

I became interested in medicinal chemistry during my undergraduate studies in Biotechnology (National University of Rosario, Argentina), where I was fascinated by the potential for chemistry to address important problems in healthcare. As I learned more about the role of chemistry in drug discovery and development, I became increasingly interested in the interdisciplinary nature of medicinal chemistry and the potential for collaboration between chemists, biologists, and clinicians to develop new therapies.

My passion for medicinal chemistry continued to grow during my graduate studies, where I had the opportunity to work on a project focused on the design and synthesis of novel small molecules for the treatment of neglected tropical diseases (NTDs), such as leishmaniasis, Chagas disease, HAT, malaria, etc., as well as for cancer. This experience solidified my interest in drug discovery and showed me the potential impact that medicinal chemistry research can have on patients' lives.

Since then, I have been fortunate to have the opportunity to work on a range of projects in medicinal chemistry and chemical biology, from designing inhibitors of infectious disease targets to developing novel chemical probes for target discovery in NTDs. The diversity of these projects has allowed me to develop a broad perspective on the field and has reinforced my passion for using chemistry to address important problems in healthcare.

What was the topic of your PhD project?

My interest in prenylated compounds, a privileged structure in nature, together with the enormous experience of my supervisor in the prenylated’s world, Prof Guillermo Labadie, led me to pursue a PhD focused on using these compounds as a basis for generating novel chemical and biological tools to expand our understanding of foundational biology, particularly regarding organisms that produce neglected tropical diseases (NTDs). Through my research, I aimed to develop new strategies for identifying and targeting NTD-producing organisms, which pose a significant public health threat in many parts of the world.

My PhD thesis was completed in 2015 at National University of Rosario, and was recognized and awarded by the Argentine Society of Organic Chemistry as the best Argentine thesis of the biennium (2015-2016). This recognition was a testament to the innovative approach and significant contributions of my research, which has the potential to drive new discoveries in the field of medicinal chemistry.

My first postdoctoral experience was in Argentina, working at the Rosario Chemistry Institute and the Institute of Molecular and Cellular Biology of Rosario. My second postdoctoral position was at the Department of Chemistry of Durham University, in the United Kingdom.

Where are you currently working and are your current research interests?

Currently, I am working at Durham University (United Kingdom) as a Research Fellow (Marie Sk''.chr('322').''odowska–Curie actions, Durham University, and the Network for Neglected Tropical Diseases).

My current research interests focus on the use of activity-based protein profiling (ABPP) to develop new strategies for identifying and targeting enzymes involved in the pathogenesis of neglected tropical diseases (NTDs). ABPP is a powerful chemoproteomic tool that allows us to selectively visualize and measure the activity of enzymes within complex biological systems, providing valuable insights into the mechanisms underlying disease.

My research in this area aims to expand our understanding of the molecular mechanisms driving NTD pathogenesis, with the ultimate goal of identifying new therapeutic targets and developing more effective treatments for these devastating diseases. I am particularly interested in exploring the use of ABPP in combination with other technologies, such as high-throughput screening and medicinal chemistry, to accelerate the discovery and development of new drugs for NTDs.

How would you explain what your research area is to non-scientists?

My research area focuses on studying diseases that are often overlooked and underfunded, called neglected tropical diseases (NTDs). These diseases affect more than 1 billion of people in low-income countries and can cause a lot of suffering and disability.

To help find better treatments for NTDs, I use a special technique called activity-based protein profiling (ABPP), which allows me to study the specific proteins in the pathogens that are involved in causing these diseases. By understanding how these proteins work and interact with each other (this is called the interactome), we can identify new ways to stop the disease from progressing and develop more effective drugs.

To help explain my research approach, I often use the analogy of archery. Just as an archer uses a bow and arrow to hit a target, I use specialized techniques and chemical probes to study proteins in the body that are involved in disease. In this analogy, the bow represents the various techniques I use, such as activity-based protein profiling (ABPP), while the arrow represents the chemical probes that I use to target specific proteins of interest. The target itself represents the sum of all the proteins in an organism, and the centre of the target is the specific proteins that I want to study. Just as an archer aims for the centre of the target, I aim to use my techniques and chemical probes to study the proteins that are most relevant to disease. By hitting these targets, I can gain a better understanding of the mechanisms behind disease and identify new ways to develop more effective treatments.

What do you like best about your work?

As many scientists in the field of medicinal chemistry, I enjoy the opportunity to make a meaningful impact on human health by developing new treatments for diseases that can have a major impact on people's lives. This sense of purpose and contribution to society can be incredibly rewarding.

Additionally, I enjoy the intellectual challenge and creativity that comes with designing new chemical compounds and developing innovative approaches to studying disease. There is always more to learn and discover in this field, which can make for a stimulating and engaging work environment. Also, I am grateful for the collaborative nature of the work, which often involves working with other scientists and researchers across different disciplines to tackle complex problems. The opportunity to work with others who are passionate about advancing scientific knowledge can be a fulfilling and motivating experience.

Of course, collaborating with other scientists and networking is also critical to successful research in this field. Finally, writing reports and publications and supervising PhD and Master students are important aspects of communicating research findings and mentoring the next generation of scientists.

What do you consider your greatest achievement in your scientific career?

It can be difficult to pinpoint a single greatest achievement in my scientific career. While I have received individual awards that I am proud of, I would say that one of the most fulfilling experiences was the day my first master's student, Dr. Jaime Isern, obtained his degree. Being able to train and mentor the next generation of scientists is incredibly inspiring and rewarding. It's exciting to see my students grow and develop their own research interests, and I feel a sense of pride and satisfaction in their accomplishments. Ultimately, they will carry on the work and push the boundaries of scientific discovery even further, and I am honoured to have played a part in their journey.

Which of your papers are you most proud of and why?

One of the papers that I am most proud of is "Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling," which was published in Frontiers in Pharmacology in 2022. This paper is particularly meaningful to me because it represents the first of a series of publications that will highlight the use of chemoproteomic tools in NTD-producing parasites, a project that I am currently leading at Durham University. Through this research, we are exploring new ways to identify and target the proteins that are responsible for causing diseases like leishmaniasis, and I am excited about the potential impact that our work could have on global health.

Porta, E.O.J., Isern, J.A., Kalesh, K., Steel, P.G. 2022. Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling. Front Pharmacol. 13, 929493. doi: 10.3389/fphar.2022.929493.

What are the features of a successful PhD student or postdoc?

PhD students and postdocs need to be self-motivated and have a strong work ethic to be successful. They need to be able to work independently and manage their time effectively. Another key feature is critical thinking and problem-solving skills, adaptability, and resilience. Also, a clear communication of ideas, results, and challenges is essential to succeed as a PhD student or postdoc. PhD students and postdocs often work as part of a larger research group, so the ability to work effectively in a team is critical for the sharing of ideas, knowledge, and resources to accomplish research goals. Finally, a love for science and a genuine curiosity about the world are key ingredients for success in a PhD program or postdoc position.

What advice would you give to someone who wants to know more about your field?

If someone wants to know more about my field, I would suggest several things: Start by reading review articles and textbooks on medicinal chemistry to gain a solid foundation of the field's principles and techniques. Attend conferences, workshops, and seminars to learn about the latest research and network with other scientists. Consider pursuing an internship or research experience in a medicinal chemistry lab to gain hands-on experience with the techniques and methods used in the field. Join professional organizations and subscribe to relevant journals to stay up-to-date on the latest research and news in the field. Finally, be curious and ask questions! The field of medicinal chemistry is constantly evolving, and there is always something new to learn.

Have you experienced any unfair situations during your scientific career? How would you advise scientists facing similar situations?

Unfortunately, unfair situations can occur in any career, including scientific research. However, if a scientist is facing an unfair situation, my advice would be to first seek support from colleagues or mentors or institutional resource, and document the situation as much as possible. It may also be helpful to reach out to relevant professional organizations or advocacy groups for guidance and resources. It is important to remember that addressing unfair situations can take time and persistence, but seeking help and speaking out can ultimately lead to positive change. I have personally witnessed and experienced unfair situations in my scientific career, and I believe it is important to seek guidance and support in such situations.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

When I first started working in a laboratory, in my very first day, I accidentally broke a mortar. But it taught me a valuable lesson - that mistakes and accidents are an inherent part of the scientific process and that it's often through failure that we learn the most. As a result, I've always believed that if you're not breaking something in the lab, you're probably not pushing the boundaries of what's possible.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

Films: Radioactive; Breaking bad (series); Perfume, the Story of a Murderer.

Books: The Disappearing Spoon: And Other True Tales of Madness, Love, and the History of the World from the Periodic Table of the Elements by Sam Kean; H2O: A Biography of Water by Phillip Ball; Vector by Robin Cook.

Which scientist do you admire the most and why?

There are many scientists who have made significant contributions to the field of medicinal chemistry, and it is difficult to choose just one. However, if I had to pick, I would say Carolyn Bertozzi, because she is a renowned chemist and biochemist who has made significant contributions to the fields of chemical biology and glycobiology. I admire her not only for her ground-breaking research but also for her commitment to promoting diversity and inclusion in science. As a leader in her field, she has inspired many young scientists to pursue careers in STEM and has worked to create opportunities for underrepresented groups in academia. Her dedication to interdisciplinary research and her ability to combine chemistry, biology, and medicine in innovative ways is truly remarkable, and I am inspired by her work and her vision for the future of science.

Which field of medicinal chemistry do you consider the most promising for the future?

Currently, there are several exciting areas in medicinal chemistry that show great potential for future developments. Some of the most promising fields of medicinal chemistry for the future include the development of targeted therapies for cancer and other diseases, the discovery of novel antibiotics and antiviral drugs to combat emerging infectious diseases, the design of new drugs for neurological disorders, proteolysis targeting chimera (PROTAC), nanotechnology-based drug delivery systems, and the development of personalized medicine approaches based on genomics and proteomics. They are all promising areas that could have a significant impact on human health in the future. Additionally, the use of artificial intelligence and machine learning in medicinal chemistry is also a rapidly growing area that holds great promise for accelerating drug discovery and development.

What would you expect to be the next major breakthrough in medicinal chemistry?

I would say that personalized medicine is one the most promising area in medicinal chemistry and, possibly, the next major breakthrough. Recent advances in genomics, proteomics, and related fields are making it possible to tailor treatments to an individual's specific genetic and disease profile. This will be further accelerated by the integration of artificial intelligence into medical development programs, which can help identify personalized treatment options based on large-scale data analysis.

How did you get interested in Medicinal Chemistry?

I grew up in a pharmacist’s family, my father, mother and my sister are all pharmacists. Since at that time I was less interested in biology, I focused to chemistry and obtained my MSc in Chemical Engineering. During my undergraduate years I joined the research group of Prof Nógrádi on natural products chemistry as a research student. After completing my thesis in Karlsruhe, Germany, I continued natural product synthesis that was extended by structural and biological studies. Natural products, ethnomedicine and the film, Medicine Man starring Sean Conory inspired me towards Medicinal Chemistry.

Therefore, I learned cheminformatics and drug design at Budapest during my postdoc years and then joined Sanofi heading a chemistry research lab in 1996. Next, I moved to Gedeon Richter and spent 14 years before moving back to academia in 2013.

Where are you currently working and what is your current position?

How did you get interested in Medicinal Chemistry?

Although I come from a family of Pharmacists (grandmother, mother, aunt, sister) after graduation in Pharmaceutical Sciences I experienced ERASMUS in the lab of Pedro Pérez at University of Huelva; Spain and “fell in love” with organic synthesis. The connection between organic and pharmaceuticals felt “natural” and synthetic. I did my PhD at the Faculty of Pharmacy, University of Porto on "Design and synthesis of antitumor xanthones"

I started my academic career along with my PhD project at Porto and after PhD did short trainings at Universidade São Carlos Brazil with Quezia Cass on enantioseparation studies

Where are you currently working and what is your current position?

I’m currently researcher at the Interdisciplinary Centre of Marine and Environmental Research (CIIMAR) and Associate Professor with Habilitation of Organic and Medicinal Chemistry of the Faculty of Pharmacy of the University of Porto.

Mostly besides teaching I’m engage in supervision, administration, outreach activities, capturing financial support, establishing and coordinating collaborations.

How would you explain what your research area is to non-scientists?

Normally, in outreach activities in schools showing some molecular models and useful microorganism in Petri plates helps to explain the drug resistance problem; but to capture the attention of young audiences I choose to show the villains and my student the heroes.

What do you like best about your work?                      

Creativity, the possibility of testing our hypothesis. Particularly in research, a good “chemical toolbox”, with a nice set of reactions, structure elucidation, analysis, and making decisions.

How would you describe yourself as a supervisor?

I currently supervise 2 posdocs, 3 PhD students and cosupervise other 5 PhD. These students are at different periods, finishing and starting and they need my full commitment. I see myself as a facilitator, in overcoming resistance (not bacterial… drawbacks that can appear in the process).

What do you consider your greatest achievement in your scientific career?

My greatest achievements are normally the last ones… organising a meeting last month gave the opportunity to young researchers of presenting their work and to attend in person after two years of virtual meetings.

Which of your papers are you most proud of and why?

In Biochem Pharmacol. 2012 doi: 10.1016/j.bcp.2011.10.004 we started our focus on overcoming anticancer drug resistance inspired in existing drugs and now we are moving to antimicrobial drug resistance and marine natural products as for example in RSC Advances, 2020, 10, 31187 – 31204 https://doi.org/10.1039/D0RA05319H

What are the features of a successful PhD student or postdoc?

To embrace Science, not to be closed in their own projects but to share and acquire different knowledge and collaborations.

What would you like to ask from other medicinal chemists?

Collaborations, strong and focus collaborations are cherished.

Have you experienced any unfair situations during your scientific career?

Not really…but we must respect decisions that sometimes are unfair at least from our point of view, but should not give up and do our best because our efforts will be recognised; resilience not only in research.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

After performing the last step of the total synthesis of a natural product, I used the wrong centrifuge tubes in a purification step and the compound spread through the apparatus; It takes a dose of resilience and problem-solving to overcome limitations.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

I still appreciate a practical book for new research students: Advanced Practical Organic Chemistry, By John Leonard, Barry Lygo, Garry Procter

Which scientist do you admire the most and why?

I would say my supervisor, Professor Madalena Pinto for her joy and contagious enthusiasm; and my students, brave young generation.

Which field of medicinal chemistry do you consider the most promising for the future?

Selective bioactivation; new bioactivation mechanisms unveil

What would you expect to be the next major breakthrough in medicinal chemistry?

The interception of chemistry and biology has render major breakthroughs in the last years; now physics and other sciences will sure contribute to increase the interdisciplinary science that is medicinal chemistry, we are assisting to major breakthrough with light-mediated mechanisms.

How did you get interested in Medicinal Chemistry?

I started to get involved in the field of Medicinal Chemistry while I was studying in Belgium, during the last year of my degree. I had the opportunity to discover how the organic chemistry that I have studied could influence and benefit the society. After synthesizing new antibiotics I changed to the field of kinases in neurodegenerative diseases which has been the topic of my PhD project. It has been a challenging but rewarding pathway since targeting the CNS is arduous.

Where are you currently working and what is your current position? 

After finishing my PhD this last April, I currently work in at CIB CSIC as a postdoctoral fellow but I am actively searching a postdoctoral position abroad to continue with my academic career. I would like to learn novel techniques like DEL, computational chemistry, DCC or PROTACS to complete my background in kinase inhibitors drug discovery, structural biology and nanoparticles. During these years we have been trying to develop new drugs for the treatment of amyotrophic lateral sclerosis and other neurodegenerative diseases. I design and synthesize new chemical compounds to target kinases, a type of enzyme that modifies other protein sometimes causing toxic consequences for the cells.

What do you like best about your work?

The best part of my job is working with other scientist and being able to directly see how my molecules interfere and change the course of the disease in cells and in animals. I like the multidisciplinary environment that I have experienced since in my opinion is the best way to expand your knowledge and your limits. Another positive aspect of being a scientist is the opportunities to meet people from different backgrounds and countries in the multiple congress, symposiums and meetings we usually attend.

What do you consider your greatest achievement in your scientific career?

I am very proud of being the most meritorious runner-up for the 2022 EFMC-YSN PhD Prize, I am aware of the great level of other PhD candidates across Europe and this has been a great honour for me. Related to my research, I enjoyed writing the paper related to multitarget compounds for Alzheimer’s disease, which was published in 2021. It was a challenging but exciting project in which I implemented target-guided synthesis. Seeing the final paper published in Angewandte Chemie and the bigger picture of the project after many years was a great reward to all the efforts done.

What are the features of a successful PhD student or postdoc?

In my experience, the most important aspect of a successful PhD thesis is being happy with your project and working in a good laboratory, with a healthy atmosphere and a great supervisor. I could not imagine overcoming all the difficult situations that happened during these years without the support of my supervisor and my colleagues. Another aspect that I have enjoyed very much is participating in dissemination activities with other scientist and also with the general public. It helps you to see other aspects of your research and make the effort to explain it to someone that is not an expert in science. Finally, I believe that scientist can really make a change so I am usually involved in research associations or federations, because I think that we have to fight for what we consider fair.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

During a short stay related to protein crystallography in another CSIC centre, one colleague of mine and I accidentally swiped the crystals that we were analysing in the synchrotron. After three years of research, it was the first time that my colleague was diffracting protein crystals but they were not his crystals but mine…

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

Related to science and dissemination, I enjoyed very much a Spanish podcast called “Catástrofe Ultravioleta”. They share very interesting stories about scientific and historic discoveries from an innovative point of view. I have, of course, seen all the chapters of the TV series “The BigBang Theory”. It is very funny to see how they picture scientists and the hilarious criticism that they make to the pharmaceutical companies. 

Which scientist do you admire the most and why?

I really admire Marie Curie and her husband Pierre. I think he stood for his wife and contributed to the recognition of the success of every woman in science after her. I am a big fan of Rafael Yuste, a Spanish neurobiologist one of the drivers of the BRAIN project. I heard one of his conferences related to neurorights which caused me a great impact.

Which field of medicinal chemistry do you consider the most promising for the future?

I think that DNA-encoded libraries have a promising future, in order to engage the target in the discovery of its own inhibitor and accelerate this process. On the other hand, I really hope that Medicinal Chemistry would be able to find a cure for neurodegenerative diseases like amyotrophic lateral sclerosis or dementias, millions of patients count on us.

How did you get interested in Medicinal Chemistry?

Medicinal chemistry attracted my interest because it is a discipline that integrates different expertises ranging from computational design and synthetic organic chemistry to biophysical and biological evaluation. 

What was the topic of your PhD project?

I received my Ph.D. degree in Chemistry from the University of Milan, under the supervision of Prof. C. Gennari, working on the rational design of highly stereoselective boron enolates using transition-state computer modeling. The developed reagent was subsequently used to synthesize Taxol and Taxotere. Both, synthetic chemistry and quantum mechanical calculations, were performed during the Ph.D. studies.

Where are you currently working and what is your current position?

In 1995, I joined Pharmacia & Upjohn, later Pfizer, and in 2006 I moved to Novartis, where I support drug discovery projects in various therapeutic areas, from early target assessment up to lead optimisation. 

What are your current research interests?

My research interests include ligand-based Fluorine NMR screening in drug discovery, the investigation of the role of fluorine in drug design, the development of novel methods for describing and comparing either fluorinated molecules or protein binding sites. 

How would you explain what your research area is to non-scientists?

My aim is to improve the efficiency of drug discovery by helping to design compounds that have a high probability of binding to the target of interest with the right molecular and physical properties to ultimately demonstrate good bioavailability and be beneficial to patients.

What do you like best about your work?

The possibility to work in multidisciplinary teams on various challenges. I like working in different disease areas with different protein families and different modalities.

What kind of skills does your work require?

Creativity with scientific rigor. Broad knowledge of all disciplines involved in drug discovery. Good communication skills and self-motivation.

What do you consider your greatest achievement in your scientific career?

Contribution to the development of drugs that have reached the clinic.

Which of your papers are you most proud of and why?

The perspective published in J. Med. Chem. (2019), 62, 2218-2224 nicely summarizes the synergy of working at the interface of different disciplines.

How did you get interested in Medicinal Chemistry?

During my chemistry studies I first fell in love with synthetic organic chemistry. Synthesizing and characterizing organic molecules was something I enjoyed a lot. In the course of my studies I then became attracted by the logic of retrosynthesis and natural product synthesis, which was then also the topic of my PhD thesis. Naturally, once you have synthesized complex organic molecules you also become interested in their pharmacological activity and the broader context of drug targets as well as pharmacokinetics.   

Where and when did you obtain your PhD diploma?

I obtained my PhD from Karlsruhe Institute of Technology (KIT) in 2006. During my undergraduate studies at University of Bonn, I decided to join the group of a freshly appointed organic chemistry professor, Stefan Bräse. Stefan was an outstanding mentor, giving every team member the feeling of pushing the boundaries and providing every support. Shortly after I joined the group, Stefan was appointed to KIT and I moved with the group. 

The topic of my PhD project was the total synthesis of the fungal natural product Diversonol which forms part of a larger group of fungal metabolites. Our goal was to apply a self-developed synthetic method to this group of natural products which in the end worked out. We published the total synthesis in Angewandte Chemie and the work was later confirmed by the Nicolaou group in an independent synthesis. Unfortunately, Diversonol turned out to have very limited biological activity, but this is also part of science. 

Where did you have your postdoc position?

For my postdoc, I had the unique opportunity to join Andy Myers group at Harvard University. This was a different universe and an enormous learning experience. Over the last decades, Andy´s group has had an immense influence on the broader field of Life Sciences. As one example, the group´s work on several classes of antibiotics has clearly highlighted the power of small molecule drug discovery. What I found particularly impressive was the combination of synthetic organic chemistry with chemical biology as well as the commitment to push translation of inventions into clinical development via startup companies.

How did you get interested in Medicinal Chemistry and Chemical Biology?

I was intrigued by the question which structural features make small molecules bioactive and relevant to biology? We then devised new principles and concepts for bioactive compound design (inspired by natural product structures, i.e. classes of compounds that are biologically relevant by definition), developed the corresponding synthesis programs (including new enantioselective catalysis methods), evaluated the new compounds in unbiased phenotypic assays, identified and validated the targets, and finally explored the most promising compounds in disease-relevant settings. This continuum of investigations defines chemical biology research leading straight into medicinal chemistry.

Where and when did you obtain your PhD diploma? 

I graduated from the University of Mainz in 1985. My thesis focussed on the development of new protecting group strategies for glycopeptide synthesis. Working in the group of Horst Kunz, I introduced the allyl ester into glycoconjugate synthesis. Afterwards, I did my Post Doc with George Whitesides at Harvard University in 1985-1986.

Where are you currently working and what is your current position?

I jointly hold positions as Director of the Department of Chemical Biology at the Max-Planck-Institute of Molecular Physiology in Dortmund and as Full Professor of Biochemistry in the Faculty of Chemistry and Chemical Biology at TU Dortmund. 

My work requires being a scientist and researcher, teacher, mentor, manager, advisor, consultant, company founder, ….. (as holds for many, if not all of my peer group).

What are your current research interests?

The underlying question described above has been a consistent motivation for my group. We are a team of organic chemists, biochemists, biologists and computer scientists which fuse these disciplines into chemical biology research. We develop new concepts for bioactive compound design (now integrating underlying principles of chemical evolution), synthesize these compounds, including the development of new methods, e.g. in enantioselective catalysis, investigate the resulting compound collections in target-agnostic phenotypic and morphological cellular assays and then identify the cellular targets and modes of actions of the new bioactive compounds, and if these are related to human disease we advance them into drug discovery. This multidisciplinary program has given rise to a “Chemical Evolution of Natural Product Structure”, and “Pseudo-Natural Products” now in preclinical investigation.

What do you like best about your work?

The freedom to work on what interests me most, and the singular moments of discovery and insight.

What kind of skills does your work require?

Most important is the ability to repeatedly generate good ideas, see underlying principles behind data sets and derive new concepts and principles from them which will then guide future research. But people skills and the ability to motivate come next. In science being a good communicator is of high importance. And, finally, a certain degree of robustness, both mental and physical, is required. Personally, for long-time success, I try to consistently operate at 95% of my maximal capacity (which requires that the 100% threshold has been identified), which leaves sufficient bandwidth to go beyond 100% on short notice and whenever required.

How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?

Currently, we are a group of ca. 25 students, Post Docs, Senior Scientists and associates. Applications by excellent Post Doc candidates are always welcome. Since I will adopt Emeritus status in the coming years, I do not accept Ph. D. students in my group anymore.

How would you describe yourself as a supervisor?

Good science needs the air of freedom to explore own ideas and to be creative, and I leave my students and Post Docs the required room. Certainly, I am demanding, and all members of my group work hard. But I will always welcome a good beer on a Friday afternoon and a barbecue on the terrace adjacent to the lab. The social atmosphere in a group is of high importance.

How did you get interested in Medicinal Chemistry?

My interest was first for chemistry and its impact on living systems, which dates from my high school days. Even so at the time I did not know what job would be the most suited for combining chemistry and biology. During my first days at university, I felt in love with organic chemistry, it sounded like making molecule was a lot like assembling a Lego set. From then I knew I wanted to work in this field and during my undergrade I was fortunate to do a 1-year internship at Infinity Pharmaceuticals in Cambridge, MA. This placement reinforced my conviction that medicinal chemist was the job I wanted to do.

Where and when did you obtain your PhD & Postdoc diploma?

I got my PhD from the University of Nottingham in 2015. I started grad school in Edinburgh and after 1 year my PhD advisor, Hon Wai Lam moved the group to Nottingham. I focused on developing novel enantioselective conjugate-additions using transition-metal as well as organocatalyst. Overall, my time as a grad student was a very good training for a future job as a medicinal chemist, as it gave me a good skillset for organic synthesis.

I did my postdoc in the lab of Barbara Imperiali at MIT. I focused on the development of inhibitors and probes applied to the study of the glycosylation pathways of Gram-Negative organisms. This was a completely different environment than my PhD lab and it served me very well to become a medicinal chemist because it prepared me for the cross-functional interactions that a medicinal chemist encounters every day. 

What are your current research interests?

I love working on precision oncology programs. It’s a field which has such a strong impact on patients.
I am also very interested in the integration of technology within the drug discovery process, from target identification, screening, hit validation all the way to clinical trial.

How would you explain what your research area is to non-scientists?

One of my favourite metaphors to describe the job of medicinal chemist is to compare to building a Lego set which needs to impact the biology of a disease. My wife being an interior designer I also use the analogy of kitchen cabinets design to describe it. If the cabinet is the drug and an apartment building being the body. You must build a cabinet that fits for one apartment only and it has to be built and assembled outside, then it has to make its way to the proper apartment. 

What do you like best about your work?

First I like the finality of our work, trying to find new treatment for patients is such a strong motivation. On a daily basis I like the high pace and the generation of large data set. Trying to solve problems with so many variables using chemistry really keeps me on my toes, so I never get bored. I feel very lucky to be able to combine work and passion, trying to solve those problems is very exciting and stimulating.

How would you describe yourself as a supervisor?

I had the chance to mentor undergrade and master students during both my PhD and postdoc. I love to share my passion for science and get others involve and able to express and try their own ideas.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

Thankfully I haven’t had anything such as an explosion, but I had a small fire once. I was heating a large flask in an oil bath, at around 200 °C (melting urea in order to use it as solvent/reagent), the oil expanded, started to overflow, and I decided to clean the surrounding of the stir plate with some hexane…of course, some got underneath the stir plate and caught on fire… 

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

 

Particular recommendation from blog: In the Pipeline: https://www.science.org/blogs/pipeline

Drughunter: https://drughunter.com/

Which scientist do you admire the most and why?

I am a huge fan or Darwin, I have always admired the idea of resilience and evolution and he is the first name associated with this theory. I also loved the idea of a 5-year trip around the world while being 22 years old.

Have you experienced any unfair situations during your scientific career?

I have been fortunate to not experience many unfair situations during my career. But working in a chemistry lab it’s hard to ignore that chemistry overall lacks diversity. I am hopeful that things are changing for the better. I am involved and I am seeing more initiatives which focus on helping people from different backgrounds to access positions in our department.

Which field of medicinal chemistry do you consider the most promising for the future

I am surely biased but integrating the latest technological progress to shorten cycle time will keep impacting more and more medicinal chemistry in the years to come.
I also thing that new modalities such as molecular glue and PROTAC will be part of the next generation of small molecules as a new efficient tool in the medicinal chemist tool kit.

What advice would you give to someone who wants to know more about your field? 

Reach out to couple of medicinal chemists and get to know the field by chatting with them. If possible, try to find a program that will give you the opportunity for placements within medicinal chemistry departments.

What would you like to ask from other medicinal chemists?

How do they prioritize SAR and decide when to keep pushing or abandon a series.
Also, how much “strictly rational” design vs empirical libraries.

What would you expect to be the next major breakthrough in medicinal chemistry?

A good maturation of the newest screening methodologies which would contribute to the delivery of high-quality hits. One key aspect is to generate lots of high-quality data which can then be combined machine learning models in order to deliver a superior hit exhibiting good parameters (LLE, selectivity…).

How did you get interested in Medicinal Chemistry?

I am trained as a pharmacist and obtained my master in pharmaceutical sciences in 1988. During my 6 months internship, I realized that, although working in a community pharmacy is an important job with a big social impact, I wanted to do something else with my life. I was attracted to research, and mostly to the chemical aspects of medicines. However, during our studies, the chemical aspects of medicines were mostly focused on the analytical aspects. Around that time, Piet Wigerinck, former CSO of Galapagos, who graduated one year before me convinced me to have a talk with his supervisor, Prof. Piet Herdewijn. Piet Herdewijn was a young professor starting up his group in medicinal chemistry and he could easily convince me to join his group. In fact, I was his second PhD student.

Where and when did you obtain your PhD diploma?

After 4 years of PhD at the Rega Institute of KULeuven in Belgium, I obtained my diploma in 1992 with Prof. Piet Herdewijn as supervisor. The Rega Institute is best known for its research on infectious diseases. That period was marked by the HIV/AIDS pandemic and the discovery of the very first nucleoside and non-nucleoside reverse transcriptase inhibitors. The medicinal chemistry group collaborated intensively with the virology group lead by Prof. Erik De Clercq, and so this was a highly interesting and stimulating environment for me. The first paper I co-authored was published in Journal of Medicinal Chemistry in 1990 on the synthesis and anti-HIV activity of 2’,3’-dideoxyribo-5-chloropyrimidine analogues. This is more than 30 years ago. Time flies.

What was the topic of your PhD project?

The period of my PhD was also the start of chemically modified antisense oligonucleotides and the early days of automated DNA synthesis. We started exploiting the extensive knowledge of nucleoside chemistry available in the group to synthesize sugar-modified DNA analogues. I synthesized several hexopyranosyl nucleoside analogues that were functionalized for automated oligonucleotide synthesis and studied their properties such as hybridization specificity and enzymatic stability. My PhD thesis was entitled: Synthesis of sugar-modified antisense oligonucleotides. It is rewarding to notice that after 30 years of huge efforts the therapeutic principle of antisense oligonucleotides is finally paying off. At the end of 2016, Nusinersen was approved for the treatment of spinal muscular atrophy (SMA).

An interesting story connected to my PhD topic is that one day my supervisor came into my lab and told me that he heard that competition had increased “a little bit”. Around the same time, the group of Albert Eschenmoser at the ETH in Zurich also started investigating the synthesis of hexose nucleic acids. His purpose was to find why nature had chosen for pentose and not hexose nucleic acids. Finally we published almost together in 1992 our findings.

Where did you have your postdoc position?

After my PhD, I belonged to one of the last classes in Belgium who still had to do military service. Next, I went as a postdoc to the medicinal chemistry research group of Prof. Achiel Haemers at the University of Antwerp, Belgium. Soon, I realized that an international experience would be beneficial and applied in Germany for the prestigious international postdoctoral fellowships of the Alexander Von Humboldt Foundation. I was lucky to be selected and worked for one year under the supervision of Prof. Günther Jung at the University of Tübingen in Germany. This was a very rewarding experience. It was the start of combinatorial chemistry and Günther Jung was translating his experience in solid-phase peptide synthesis to applications in combinatorial chemistry. Four years ago, a large group of his PhD students and Postdocs celebrated his 80th birthday with a big party in Tübingen.

Where are you currently working and what is your current position?

Currently I am full professor of medicinal chemistry at the University of Antwerp in Belgium. Next to that I am also the Dean of the faculty of the university and until the end of 2019 I served the European Federation for Medicinal Chemistry in several roles.

What are your current research interests?

One of the major research lines in my group is the discovery of inhibitors of novel types of regulated cell death (ferroptosis and necroptosis) and their application in different animal disease models. Currently, I am also involved as medicinal chemist in a large collaboration financed by the EU-IMI programme to discover novel drugs to treat infections caused by mycobacteria. We are targeting both multiresistant tuberculosis (RespiriTB) as well as infections caused by non-tuberculous mycobacteria (RespiriNTM). Next to that, I am also interested in applications of biorthogonal chemistry for bioimaging and irreversible serine protease inhibitors as chemical tool compounds.

How would you explain what your research area is to non-scientists?

That is a very good point. Science communication to the general public that is paying for our research is extremely important. I indeed often get the question from non-scientists what I am doing the whole day. I usually start by explaining that a university professor has two main tasks: teaching and scientific research. And I add that because of that we don’t have as much holidays as the students. I try to explain that medicinal chemistry deals with the chemistry of medicines and that we make novel molecules that eventually one day can become a drug. The general public also needs to understand that discovering new drugs is a very time- and labour intensive process, but that even small steps that learn us what is the relation between the chemical structure and the therapeutic activity, how a molecule works at the molecular level and how this can influence a disease is important for the field. Nowadays, people more easily understand what Covid-19 is and how detrimental an infectious disease can be. They see the importance of having treatment and prevention options and the need to prepare for a next pandemic. I try to explain them that resistance to existing antibiotics is becoming a major threat and that untreatable bacterial infections is one of the next big challenges.

What do you like best about your work?

In medicinal chemistry, you design and create something new for the benefit of human health. This is in contrast to many other scientific disciplines where you analyse already existing things. I still remember the excitement during my PhD when you synthesize your first molecule that until then never existed on earth before.

What kind of tasks does your work involve?

Currently I am not working in the lab anymore. Next to teaching, an important task is to find money for research by writing national and international grant applications. Successful execution of these research projects is only possible by recruiting highly talented PhD students and postdocs and then guide them towards the research goals. More and more, research is done in multidisciplinary consortia so collaborative skills and networking are highly important as well. As a dean of the faculty, I am furthermore responsible for research policy, personnel and students, and administration. Luckily the latter is limited because I am fortunate to have a very efficient dean’s office. By far the most important task as a dean is to attract bright and motivated young professors.

What do you consider your greatest achievement in your scientific career?

It is difficult to name one. During my PhD we were among the first to incorporate sugar-modified nucleosides into oligonucleotides. As a young professor we pioneered the field of DPP4 inhibitors, which is now a well validated target with several inhibitors on the market as antidiabetic medicines. More recently we published several cell death inhibitors, among which the most potent ferroptosis inhibitors with interesting properties in in vivo disease models. I also felt very honoured to have served the European Federation for Medicinal Chemistry (EFMC) as an executive board member for 11 years, being the president from 2015 until the end of 2017.

Which of your papers are you most proud of and why?

One of my first papers. Augustyns, K. et al. Incorporation of Hexose Nucleoside Analogues Into Oligonucleotides - Synthesis, Base-Pairing Properties and Enzymatic Stability. Nucleic Acids Research 1992, 20, 4711-4716.

How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?

I am the head of the research group of Medicinal Chemistry at the University of Antwerp (UAMC) that consists of around 25 researchers. I am directly supervising 3 PhD students and 9 postdocs. Currently we are not recruiting, but we had several open positions in the last two years.

What are the features of a successful PhD student or postdoc?

Of course you should have an excellent knowledge of organic and medicinal chemistry, but even more important is passion for science, ambition and the desire to obtain as much experience as you can through international mobility.

What was your first EFMC experience?

My first EFMC experience must have been as a young postdoc at the International Symposium on Medicinal Chemistry (EFMC-ISMC) in 1994 in Paris. I still remember this as an overwhelming and enthusing experience. As a young scientist I had never imagined to be one day also on stage in front of such a large group of medicinal chemists. In 2002 we decided to restart the Medicinal and Bioorganic Chemistry Division of the Royal Flemish Chemical Society (KVCV). One of the first things we did was to contact Edmond Differding, who was at that time the president of the Medicinal Chemistry Division of SRC, the chemical society of the French speaking part of Belgium. He stimulated us to apply for EFMC membership and in 2004 at the council meeting we were approved and I became EFMC council member. In 2009, when Gerhard Ecker became EFMC President, he asked me to apply for Secretary. That was the start of a 11-year long exciting journey in the executive committee of EFMC with among others the organisation of EFMC-ISMC in 2010 in Brussels and the Frontiers in Medicinal Chemistry symposium in 2015 in Antwerp.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

“Breaking Bad”, although I do not recommend anyone to perform the chemistry that Walter White is doing.

Which scientist do you admire the most and why?

Paul Janssen, one of the pioneers of medicinal chemistry and drug discovery. He really brought our field to where we are now and he was and still is an inspiration to many scientists in Belgium and around the world.

Have you experienced any unfair situations during your scientific career?

No. On the contrary, I am very grateful for all the chances that I got and I am most thankful to all my collaborators

Which field of medicinal chemistry do you consider the most promising for the future?

The challenges in the field of infectious diseases are enormous. Not only we need more and better antivirals but we also badly need novel antibiotics to treat infections caused by multiresistant bacteria.

How do you see the future role of EFMC?

As a scientific federation EFMC has to bring people together around excellent science. In a scientific discipline such as ours that is highly dependent on multidisciplinary collaborations this will always remain an important objective for the future of medicinal chemistry and chemical biology.

How did you get interested in Medicinal Chemistry?

I still was in high school when a medical doctor, friend of my family, suggested me to learn medicinal chemistry when discussing together of my desire to understand how drugs work in patients. Accordingly, despite choosing synthetic organic chemistry, I made my thesis on the synthesis of a non-natural amino acid and I learned all the associated biology and effects of the statins on the body. That was the reason for which I joined a pharma company as my first job despite having had offers from other branches of chemistry much closer to home.
In such a way I learned biology and pharmacology on the job and, a few years later, I also completed my pathway with a degree in medicinal chemistry.

Where are you currently working and what is your current position?

I currently work for Evotec in the Levi-Montalcini campus in Verona. I am VP of the Medicinal Chemistry I department and I manage a group of about 45 people in the larger Evotec chemistry community, whose mission is to discover and develop highly effective therapeutics and make them globally available to the patients who need them 

How would you explain what your research area is to non-scientists?

The discovery of a new drug is a long process, made by many small steps with a lot of potential hurdles and roadblock to overcome. You may want to see it as cross-country race in a rainy day, but I do prefer to see it like a chess game in which you plan in advance the move to overcome the resistance of your opponent until the final goal is met.

What do you like best about your work?

Challenges and diversity. Every day you discover a novel potential routes to achieve your final target but also new obstacles along the path and you need to fix these potential issues. Every day you have new things to do as the disaster is always behind the corner and only a few molecules can survive the entire path till the end.

What kind of skills does your work require?

Being a drug hunter requires definitely vision, flexibility and resilience.

I remember a dialog in an old movie where the two characters speak about crossing a river “I need a man with very special qualities to lead. He's got to be tough enough to do it and he's got to be experienced enough to do it. Plus, one more thing. He's got to be dumb enough to do it... Start getting ready”.

To achieve a potential drug, you need to plan your strategy and your tactics very well, and you need to be flexible to overcome all the roadblocks that you might find on the road. Plus, you need to be resilient enough as many of your molecules will definitely fail. Only a tiny number will get to the finish line and you know that in advance. For that your expertise if critical, to “take care” of these ones as these be the potential ones to finish in the MD list and to arrive to the patients that need them and to their beloved ones. 

Which of your papers are you most proud of and why?

Considering the fact that I only worked in the industrial environment, I am really proud of my more that 130 peer-reviewed articles and patents. Among them there is a J.Med.Chem that I love the most. It belongs to the discovery of a DA D3 antagonist. That was done in a highly competitive field with a very crowded IP area. It came after a previous closure of the research project and it contains the molecule which reached the proof of concept within humans following PET studies. 

Which scientist do you admire the most and why?

The first name which comes to my mind is the one of Dr. Tadataka "Tachi" Yamada. And this is not only as he recently passed away, but as he was an inspiring figure for me. He was a Japanese-born American physician and gastroenterologist and I met him when he was Chairman of Research and Development at GlaxoSmithKline. Being a scientist, Tachi fully understood the inherent difficulties of the research programmes. He was also an inspiring manager, whose focus was always on the patients pushing to make things with a great sense of urgency. I had the pleasure to meet him multiple times in my role of project leader. Despite his high position within the company, he had always time to look after the research programs, to give great suggestions and to also understand the tiny details of the projects. And one of the things that makes me proud is the co-authorship of a patent with him. 

Which field of medicinal chemistry do you consider the most promising for the future?

Medicinal chemistry is a continuously evolving science. It is made by great expertise, learnings from the past and always with an eye well aimed at the future. It has the capability to retain all the goods from the different things that have popping up during these years. In my humble opinion, the most promising and challenging thing that medicinal chemistry is facing is the impact of Artificial Intelligence/Machine Learning. This will surely help the scientist to achieve their targets and objectives with shorter timelines, in more efficient way and in an always “greener” environment. But this future is not far. This future is now and we are ready for this new adventure 

How did you get interested in Medicinal Chemistry?

During my Bachelors, I became fascinated by the way in which molecules interact and how humans, using rational design, can purposely modulate their behaviour.

Where and when did you obtain your PhD diploma?

I did my PhD in the lab of Prof. Dr. Stefan Günther (Freiburg, Germany). I obtained my diploma in 2014.

What was the topic of your PhD project?

The research in my PhD focused on implementing and applying computational methods for the identification and characterisation of small molecules modulating protein–protein interactions, in particular bromodomains. As part of my PhD, I deepened my knowledge in virtual screening, cheminformatics, and structure-based drug design among others.

Where did you have your postdoc position?

I did my postdoc in the lab of Prof. Dr. Alessio Ciulli (Scotland), working on PROTACs and targeted protein degradation. I implemented and applied molecular dynamics and structure-based drug approaches to study and modulate the mode of action of small-molecule degraders.

Where are you currently working and what is your current position?

Since mid-2018 I work as a scientist in computational drug design at Roche (Switzerland). I support portfolio projects especially in pre-clinical stage, i.e. from early target assessment up to lead optimisation, covering diverse therapeutic areas.

What are your current research interests?

I am particularly interested in new therapeutic modalities that challenge undruggability, for example in the fields of targeted protein degradation, RNA-targeting, or protein–protein interaction modulators, and in investigating how computational methods such as machine learning, artificial intelligence, and molecular dynamics, can facilitate that.

How would you explain what your research area is to non-scientists?

I work in the early stages of drug development designing molecules with the help of computers. Hopefully, some of those molecules follow their path to clinical trials and, eventually, cure diseases.

What do you like best about your work?

The possibility to work with highly knowledgeable scientists and the constant challenge of innovating new medicines.

What kind of tasks does your work involve?

I use all sorts of computational methods with two goals: first, to study how proteins and small molecules interact and behave, and second, to identify and design new molecules with desired biological activities and appropriate physicochemical properties. For these tasks, I use machine learning, artificial intelligence, molecular dynamics, quantum chemistry, virtual screening, cheminformatics, Free-Wilson analysis, etc.

What kind of skills does your work require?

I believe a computational chemist can benefit the most from combining a wide range of technical and behavioural skills, including programming; a sound understanding of quantum mechanics and non-covalent interactions; machine learning methods, and capabilities for spatial vision and chemical pattern recognition, along with perseverance, curiosity, and a good amount of creativity.

What are the features of a successful PhD student or postdoc?

I would say that important features include not being afraid of failure, not getting obsessed with success, not avoiding challenges, and being always open to connecting with other scientists and learning new complementary skills.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

I very strongly recommend Derek Lowe’s blog “In the pipeline”, in which he writes mostly about medicinal chemistry topics (https://www.science.org/blogs/pipeline). I also keep myself up to date about the biotech world and the pharmaceutical industry by checking regularly Fierce Pharma (https://www.fiercepharma.com/).

Which scientist do you admire the most and why?

I admire scientists with the ability to communicate science to non-specialised audiences in an accurate yet appealing manner.

Which field of medicinal chemistry do you consider the most promising for the future?

I think that in the next few years we will see drugs in the marked that exploit the targeted protein degradation concept, such as PROTACs and molecular glues, to treat diseases.

What would you expect to be the next major breakthrough in medicinal chemistry?

I expect a revolution in medicinal chemistry by further exploiting artificial intelligence, machine learning, and predictive structure-based drug design approaches.

Where and when did you obtain your PhD diploma?

I obtained my PhD in “Chemical and Pharmaceutical Sciences” at the University of Siena, Italy in the group of Professor Maurizio Botta. It was the beginning of 2017.

Where are you currently working and what is your current position?

I am currently working for the French company Discngine, in Paris. Discngine develops and provides state-of-the-art IT solutions, mainly for customers involved in life science R&D.

The title of my position is “Senior Consultant”, which, even if it does not seem to tell much, is a pretty good description of what my duties are- helping our customers with, well, a little bit of everything!

What do you like best about your work?

There are multiple aspects I love about my work. For starters, it is never boring! I have the possibility to help our customers in many different areas: from designing a custom solution to handling the administration of an application, to give training on various software, to provide scientific and technical support, to suggest and implement new ways for integration and automation… as I said – a bit of everything.

Another aspect I really like about my job is that it gives me the possibility to interact with many smart and talented people, both co-workers and customers. This often results in producing enriching experiences, allowing me to continuously grow.

Finally, it is really rewarding when I see a customer heavily relying on a piece of work I have done, or helped with. It really shows how much important what we do is.

What kind of tasks does your work involve?

See the previous answer for some examples. More in general, the kind of tasks my work involves are all around the ideation, design, implementation, management, and maintenance of custom IT solutions deployed at customers’ sites. All of this without forgetting the “human factors” as engagement and support of the user community.

What kind of skills does your work require?

My work requires a broad range of competencies. Of course, there is the need for a solid scientific and technical base, but that’s not all. Particularly important skills are also in presentation, project management and people management. It is important to have the capability to quickly grasp - and keep in mind - the “big picture”, so that one can better proceed with all the steps I have mentioned in the previous answer. Mental elasticity is finally crucial; not only is the fundamental to understand the needs, but also what is required to adapt a project when it has already started. In a real-world scenario, we need to be prepared to navigate through an ever-changing landscape of possibilities. Be able to steer in time is the key between success and failure.

What are the features of a successful PhD student or postdoc?

That depends on what one intends with “successful”. Success and sense of achievement are strictly personal feelings. Therefore, my answer here is based purely on my personal idea of success – which, in the case of a PhD student or postdoc, is to put themselves in the best conditions to proceed towards what they would like to do with their next steps. Based on such premise, I would say that to be successful they should be able to not think only about science. They should be able to think about their career path, to create opportunities for themselves, to not waste any occasion to interact with other scientists as well as not-scientists. So, translated into feature, I think that I could say: “communicative planner”.

How would you describe yourself as a supervisor?

I think that many of the ex-students I supervised while working at the university would agree on these 3 words: “tough but fair”. I believe it fits.

Which field of medicinal chemistry do you consider the most promising for the future?

The usage of AI-assisted computational methods to reliably predict 3D protein structures.

How did you get interested in Medicinal Chemistry?

I have been interested by chemistry since I was a little girl. Maybe it was the “little chemist box” that my mum had offered me, maybe it was something I read somewhere. It is difficult to know. Anyhow, sometime ago, I found an essay, “redaction” in French, that I wrote when I was eight years old, stating that I wanted to become a chemist to make new medicines to cure diseases. Over my study, I got more and more interested by organic chemistry and its application to create molecules of biological interest.

Where and when did you obtain your PhD diploma?

For my PhD, I moved really far away from my home country, France. After spending 4 years in the beautiful country of New Zealand, I completed my PhD diploma from the University of Auckland in November 2010.

What was the topic of your PhD project?

During my PhD in the research group of Prof. Brimble, I studied the synthesis of natural products and focused on the synthesis of the spiroimine unit of the spirolide family of shellfish toxins.

Where did you have your postdoc position?

After my stay in New Zealand, I returned to the North hemisphere and performed an industrial postdoc at the Novartis Institute for Biomedical Research in Basel in Switzerland. During my time at Novartis, I developed a new class of cyclic peptidomimetics and started my career in the pharmaceutical industry.

Where are you currently working and what is your current position?

Since 2015, I am working for AstraZeneca as part of the Medicinal Chemistry Department of Research and Early Development, Cardiovascular, Renal and Metabolic. During this time, I have been working in two different set-ups and locations. First, I was located in Dortmund in Germany in the AZ-MPI Satellite Unit, which was fully integrated in the research group of Prof. Waldmann. We were three AstraZeneca scientists embedded in the MPI with a focus on assessing New Modalities to address challenging targets such as PPIs and Transcription Factors. Then, I moved to Sweden to work in the AstraZeneca site in Gothenburg as a Research Scientist in Medicinal Chemistry focusing on small molecule drug discovery programs for liver diseases. After a part time rotation of few months in the DMPK department working as a DMPK Design Leader, I have recently been promoted to Associate Principal Scientist.

What are your current research interests?

My current research interests are focused toward integrating small molecules and New Modalities to address challenging targets. Further, I have a strong interest for synthetic and medicinal chemistry with broadening towards chemical biology to solve key questions on how to move forward novel chemical entities towards drug-like compounds. In the bottom of my heart, I still have a strong interest in Natural Product and the total synthesis of complex molecules which I found very fascinating.

What do you like best about your work?

The teamwork is a critical part of how new medicines are discovered. Bringing together scientists with different expertise to work in close collaboration on a drug discovery project is the part of my job that I truly enjoy the most. Exchanging knowledge, making things progress and solving problems are what wakes me up in the morning and motivates me.

What kind of tasks does your work involve?

My work is about designing new molecules with better properties to reach their targets. I work simultaneously in the laboratory performing the synthesis of novel chemical entities as well as in the design, analysis of data generated by the research project. Overall, my daily tasks are quite diverse from lab work, to brainstorming and project meetings which is something that I really enjoy.

What kind of skills does your work require?

In general, a medicinal chemist working in industry needs to have a strong background in organic chemistry while over the years broadening his/her expertise in chemical biology, diseases understanding and DMPK. From a soft skill perspective, it is very important to be creative, have good problem-solving skills and a strong motivation and commitment to advance drug discovery programs within the required timelines.

Which of your papers are you most proud of and why?

I am proud of my publications record from my PhD which gave a good overview of the work I performed during my PhD study, including the first review on the “Spiroimine shellfish poisoning (SSP) and the Spirolide family of shellfish toxins” published in Natural Product Report. More recently, I am very proud of our last JACS publication on “Macrocyclic Modalities Combining Peptide Epitopes and Natural Product Fragments”. It is a project that I lead and work on from the very beginning with a great team of postdoc and master students in the AZ-MPI Satellite Unit. We had to solve many challenges, performed a tremendous amount of work in the lab and collaborate with different scientific experts to achieve this research and access new class of modalities to address challenging targets.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

When I was in New Zealand, I used to perform multiple Birch Reductive Alkylation with potassium metal, a highly flammable metal! Unfortunately, New Zealand is a very humid country, especially Auckland located in a narrow strip of land between the Pacific Ocean and the Tasman Sea. One day while I was quenching the left-over of my potassium metal, I used a pissette of isopropanol which unfortunately had slowly suck water from the air over time, and this started a fire. My colleagues and I were able to contain the fire but it was a truly impressive experience for a young PhD student that I was, at that time. Since then, I am a master of working under anhydrous and dry conditions.

What would you expect to be the next major breakthrough in medicinal chemistry?

I think Artificial Intelligence (AI) will play a critical role in Medicinal Chemistry allowing to design faster new molecules for a given target, to answer key questions and advance drug discovery. It would allow to analyse and extract trend from large dataset in order to learn and make evolve our design and understanding of the DMPK challenges.

The silo between small molecules and larger New Modalities will slowly fade to allow to access the right modality for the right target. A better understand and knowledge on how to solve key challenges of larger molecules would allow medicinal chemists to advance these New Modalities toward drug-like compounds with required properties to reach and influence their target of interest in human.

Picture from the lab:

Where and when did you obtain your PhD diploma?

I obtained my PhD in a collaborative programme between GlaxoSmithKline and the University of Strathclyde in 2014. I was very fortunate to work with an academic (Professor Colin Suckling) and industrial supervisor (Mr John Pritchard) who both had many years of drug discovery experience and were very supportive and motivational.

What was the topic of your PhD project?
My PhD was focussed on the development of integrin antagonists as potential treatment options for people with Idiopathic Pulmonary Fibrosis (IPF). I was able to publish some of my work and see one of the molecules identified during my PhD progress into the clinic and be ultimately be given to patients with IPF.

Where are you currently working and what is your current position?

I still work in GlaxoSmithKline, I am a Scientific Leader and GSK Associate Fellow within the Medicinal Chemistry organisation based in Stevenage, UK. My current role is to lead the GSK medicinal chemistry side of a joint research collaboration with Kymera Therapeutics to discover new E3 ligase binders that can be incorporated into PROTAC molecules.

What are your current research interests?

I am really interested in the field of Targeted Protein Degradation. This is a relatively new and rapidly expanding area and it is exciting to see the progress of various PROTACs into the clinic. I am excited to see what the future will be for these large molecules. 

What do you like best about your work?

I love the fact that every day when I come into work, I face a new challenge. This could be a practical chemistry hurdle or something that is related to the programme I am working on and can only be solved by involving the wider matrix team including biologists and DMPK scientists. This helps to keep me on my toes and maintain my motivation to see programmes progress towards decision points.

What do you consider your greatest achievement in your scientific career?

The identification of GSK3008348, a potent and selective αvβ6 integrin antagonist that reached Phase 2 clinical trials. I worked on this programme for several years and experienced the progression through the entire drug discovery process from hit to lead through to candidate selection and ultimately the clinic. This evolution involved a number of different parts of the organisation, however, to be the chemist that designed and first synthesised GSK’348 is something that I am particularly proud of. Learnings from this programme were used to subsequently progress an oral programme to candidate selection as well.

Which of your papers are you most proud of and why?

In 2019 I published a paper entitled Targeting IRAK4 for Degradation with PROTACs. This was a programme that I lead with a small team of chemists and biologists from concept to decision point in less than 9 months . The work was then published within a year after the first degrader was identified. The field of Targeted Protein Degradation is a hot topic at the moment and this paper has gained many citations and has allowed me to present the story at various fora. Decisions we make are often fraught with uncertainty and the risk of being incorrect. So it is important to celebrate good decisions rather than lucky ones and I think this is one of many examples that demonstrates the smart risk-taking culture we have at GSK. ACS Med. Chem. Lett. 2019, 10, 7, 1081–1085.

How would you describe yourself as a supervisor?

I would like to think I am motivational and someone that seeks opportunities for supervisees to grow and develop themselves. I like to pass on the experiences I have had, both good and bad, and hopefully help to guide the careers of fellow medicinal chemists.

How did you get interested in Medicinal Chemistry?

I came first into contact with molecules that interfere with a biological system during a Biology lesson at school. Then we were tasked to write an assay-like text about antibiotics. A glimpse into lexica showed fascinating molecules and fascinating modes of action. This fascination never died, but shifted over the years to the question how to find such molecules in the first place.

Where and when did you obtain your PhD diploma?

I obtained my PhD in the group of Prof. Christa Müller (University of Bonn) in 2007. The topic of my PhD project was the design and synthesis of nucleotide mimetics as ectonucleotidase inhibitors.

Where did you have your postdoc position?

In the groups of Prof. Christa Müller (University of Bonn) and Prof. Jonathan Hall (ETH Zürich)

Where are you currently working and what is your current position?

I am currently a research group leader at TU Dortmund University.

What are your current research interests?

My group is working on the technology of DNA-encoded screening libraries. Basically, we are wondering how to populate the chemical space of these libraries. Is there something like an ideal screening library? In the light of the theoretically synthesizable chemical space, design of screening libraries is a daunting and intellectually stimulating task. Yet, finding novel biologically active chemical matter on a challenging target is so highly rewarding. 

What do you like best about your work?

The freedom to pick a scientific problem and the freedom to walk new ways to work on this problem. A fantastic aspect of a small molecule screening platform technology is that you can venture into many (though certainly not all!) biological targets.  

What do you consider your greatest achievement in your scientific career?

There is not the one greatest achievement, but rather a gradual learning process how to combine best the different scientific disciplines required for library design, screening, and then the follow-up once a molecule has been identified.

Which of your papers are you most proud of and why?

Difficult to answer, but I would say they fall into the category of “first-time disclosures”, and they raise a lot of questions that need to be answered in further studies. I would pick the identification of a microRNA-lnc-RNA interaction by a chemical biology strategy (Nat Chem Biol, 2015), the demonstration that a certain DNA design enables a broad chemistry scope on oligonucleotide conjugated starting materials (Chem Sci, 2017), the observation that micelle-promoted catalysts enable on-DNA reactions (J Am Chem Soc, 2019), and the identification of TEAD-YAP inhibitors from a small, designed DEL (ACIE, 2020).

What are the features of a successful PhD student or postdoc?

Curiosity and passion, and a lot of discipline and affinity for the written word.

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

Nothing to report here. I am sorry. DNA and RNA do not explode, they die a silent death.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

I enjoy reading the blog “In the pipeline” by Derek Lowe. A must-read is the book “In search of the magic bullet”.

Which scientist do you admire the most and why?

I would rather say that I am fascinated by the early era of drug research. How was it possible at all to venture into trying to cure disease with so little knowledge about physiology and toxicology, and they did not even have an NMR machine to fully and timely understand what they were making. Did nobody tell these researchers that drug research is impossible under these circumstances?

Which field of medicinal chemistry do you consider the most promising for the future?

I do not know whether it is the “most” promising field, but in my opinion the modulation of intracellular protein-protein interactions holds much promise, and with technologies that enable handling unprecedented chemical space - be it virtual or real - I hope we will witness more breakthrough stories in this field.

What would you like to ask from other medicinal chemists?

Don´t underestimate the impact of technologies but readily embrace them, and the value of innovative chemistry for compound design.

This time, our #Iamamedicinalchemist is no other than the EFMC President for the three years to come: Prof. Rui Moreira (University of Lisbon, Portugal). Get to know him better by reading the below interview.

How did you get interested in Medicinal Chemistry?

Chemistry and biology were my favourite topics in high school, which led me to choose pharmaceutical sciences when I entered university. When I first studied medicinal chemistry as a second-year student, I was immediately fascinated how chemistry could be used to address almost any major medical need. This passion was decisive when it came to decide how to develop my scientific career.

Where and when did you obtain your PhD diploma?

I obtained my PhD degree in pharmaceutical chemistry at the University of Lisbon in 1991, under the supervision of Professor Eduarda Rosa.

What was the topic of your PhD project?

My research topic was the design and evaluation of novel prodrugs for anticancer agents. I was particularly interested in studying the mechanisms of chemical and enzymatic activation of these prodrugs, and to determine the structure-reactivity relationships that could be used to the design prodrugs with improved drug delivery. This was an exciting project that brought together medicinal chemistry and the principles of physical organic chemistry.

Where did you have your postdoc position?

While not having a formal postdoc position, I did my postdoctoral research with Professor Jim Iley, at the chemistry department, The Open University, UK.

Where are you currently working and what is your current position?

I am a full professor of medicinal chemistry at the Faculty of Pharmacy, University of Lisbon, where I run a laboratory with ca. 20 people comprising research associates, postdocs and students.

What are your current research interests?

My background in physical organic chemistry led me to be interested in the design of covalent inhibitors and activity-based probes for target identification, where understanding the intrinsic reactivity associated to this type of compounds is fundamental to modulate their selectivity. Another major research topic in my group is the development of anti-infectious agents based on dual-targeting approaches as a strategy to overcome drug resistance, with a focus on parasitic diseases (e.g. malaria) and tuberculosis. Finally, we are also interested in developing tumour-activated prodrugs that use specific cellular signatures (e.g. iron level, hypoxia and oxidative stress) as triggering mechanism to release the parent drug.

What are the features of a successful PhD student or postdoc?

Be passionate about the research project, but always with a critical mind. Do not be afraid to ask questions, because there aren’t silly questions in Science. 

How would you describe yourself as a supervisor?

Supervising students goes beyond providing scientific guidance. Mentoring is crucial for career development, and I always encourage and motivate students at a personal level when problems arise during their projects.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

My recommendation goes to the EFMC website and EFMC YouTube channel, what else?

Which scientist do you admire the most and why?

Marie Curie comes first in my list of scientists I admire. Not only for her contribution to the use of radiation in medicine, setting the stage for the modern cancer therapies and imaging/diagnostic tools that help to save lives every day. But, even more importantly, for her perseverance at a time when being a woman was a limitation to scientific and academic success.       

What would you expect to be the next major breakthrough in medicinal chemistry?

CRISPR–Cas will soon become a mainstream drug discovery tool, particularly useful to identify target molecules for precision medicine. Gene editing with CRISPR–Cas provides a unique opportunity to determine which genes and proteins can cause or prevent a specific disease, thus paving the way for the development of tailor-made drugs for unmet medical needs. In addition, chemical probes that can enable a highly precise spatiotemporal control of CRISPR-Cas machinery are also expected to revolutionise the therapeutic use of this technology. 

Our first interviewee for 2021 is the winner of the EFMC-YMCS 2020 presentation prize, Ms Jessica Reynolds from the University of Oxford, United Kingdom. She is currently writing her DPhil thesis and has been awarded the EPSRC Doctoral Prize, allowing her a further six months after hand in to complete her work with Professor Stuart Conway, and explore new ideas.

What is the topic of your PhD project?

How did you get interested in Medicinal Chemistry?

How did you get interested in Medicinal Chemistry?

I have a MSc in Pharmaceutical Biotechnologies from the University of Bologna. When attending the final year in the program, thanks to some compelling lectures, I got interested in the subject of drug discovery. However, I have to say, It was computational molecular modelling that sold me the discipline.

How did you get interested in Medicinal Chemistry?

I have always been interested in treatments for people and animals. As a young girl, I was curious and wanted to understand how the body works, but it wasn’t until my first year at University where I studied natural science that I truly discovered the beauty of how one can explain biological processes if one understands molecular interactions and chemical reactivity. This ignited my passion for medicinal chemistry. 

Where and when did you obtain your PhD diploma?

At Gothenburg University in 1999 under the supervision of Prof. Stig Allenmark. My PhD project was about Bio-catalyzed asymmetric oxidation of sulfide containing organic molecules using halo-peroxidases.

Where did you have your postdoc position?

At The Scripps Research Institute in La Jolla, San Diego, US, studying asymmetric metal-catalyzed oxidation under the supervision of Prof. Barry Sharpless

What are your current research interests?

I am deeply passionate about drug design and how to get all required features into one molecule. I also believe strongly in innovation to help get potential medicines to patients – for example, the integration of various chemical modalities, targeted drug delivery, machine learning for drug design and drugging RNA using small molecules. I’m also interested in how we can transform our business into an environmentally more sustainable way of working.

What do you like most in your job?

The people I work with – within AstraZeneca and as part of our external collaborations, being surrounded by so many skilled, smart people working together to find solutions and innovations. I also like the variation and that I see a true meaning and mission in what we try to achieve.

What kind of tasks does your job include?

I lead a department of 60+ medicinal chemists and have access to a larger group of external synthetic chemists to support AstraZeneca’s pipeline in the Cardiovascular, Renal and Metabolism disease area. This means I oversee the strategic direction and prioritisations, I sit on the Research Board representing Chemistry and on the disease area leadership team. I also sit on the AstraZeneca Global Chemistry Leaders forum to guide the direction of chemistry for the company. I have a tremendously strong team so a major part of my time is spent on guiding and supporting them and removing obstacles, so they can focus on the core project deliverables. I truly enjoy seeing people I work with develop and taking on new challenges and succeed. We have also a number of students and post-docs who I try to stay in contact with and support. I’m involved in collaborations, either as a joint steering committee member or as direct scientific discussion partner. I’m also directly involved in one of our pipeline projects where we utilise a peptide chemistry approach. I spend time at external meetings, as a committee member and on publications. My job is overall very varied.

What kind of skills does your job require?

An ability to act as a respected leader by listening, having trust in others, ensuring clear communication and respect for individuals and different opinions. It requires a focus on science, and a strong core expertise in organic and medicinal chemistry. I also need to continue to build network and relationships. 

What do you consider your biggest achievement in your scientific career? 

My biggest achievement is the inventorship of a FLAP inhibitor which is in trials in the clinic. I led the chemistry from the very start of the programme until late lead optimisation, when I handed over to one of my direct reports. To present this molecule as a first-time disclosure at ACS 2018 was a special feeling. I’m also proud to have gained the trust to lead my colleagues as head of medicinal chemistry for the past six years. Now I look forward to seeing us deliver compounds from the pipeline we have built. Finally, it’s far from my achievement but I feel blessed to have been in the Sharpless lab when the Cu-catalyzed click reaction was discovered and then witnessing how it has impacted across many areas of science.

Which paper of yours you are the proudest of and why?

The 2019 Journal of Medicinal Chemistry back to back papers on the discovery of our FLAP inhibitor. Also, our review of New Modalities for Challenging Targets in Drug Discovery in Angewandte Chemie 2017 has been read and cited by many.

Which field of medicinal chemistry do you consider the most promising in the future?

Our area is full of future promise. For example, I see protein degradation by various mechanisms beyond just PROTACs to be an expanding area. In addition, the advancements in using small molecules to drug RNA and RNA/protein interfaces opens a unique opportunity. Finally, we will see major impact from machine learning and artificial intelligence (AI) in both synthesis and design which in combination with automation and miniaturisation will speed up the discovery phase of drug discovery.

What would you guess to be the next major break-through in medicinal chemistry?

I believe this will be in the area of protein regulation on the RNA level using oral small molecules to open up the druggability space for small molecules and to circumvent some of the challenges with nucleotide-based therapies. This field moves fast and the successful strategies and design criteria’s will become more evident as we learn more.

How did you get interested in Medicinal Chemistry?

The research areas that I was involved in for my master and PhD theses work and postdoctoral training were not Medicinal Chemistry. However, I was fortunate to be trained in two fields, organic chemistry and mechanistic enzymology, by some of the greatest pioneers and erudite scientists in these fields. So when I began my own lab and launched a program to develop technologies that would allow researchers to decode the biological behavior of natural reactive electrophiles with precision, I became more and more aware of how these accumulating data in this field and our own insights directly impinge on covalent drug design. So we started thinking about understanding the precise mode-of-action of emerging electrophilic pharmacophores. This avenue ultimately drew me further into medicinal chemistry and I became very excited about how our work can directly contribute to this field.

How did you get interested in Medicinal Chemistry?

It was at the beginning of my scientific career, when I was just a PhD student. I became interested in the interface between chemistry and biology and more concretely and how the, at that time incipient, molecular modelling methods, might contribute to the understanding of the mechanism of action of drugs.

Where and when did you obtain your PhD diploma?

I obtained my PhD diploma in 1982 in the Autonomous University of Barcelona. The topic of my PhD was the study of differential molecular determinants of MAO-A and MAO-B inhibitors using computational approaches.

Where do you work at the moment and what is your current position?

I am currently director of a Research Program on Biomedical Informatics, which is a joint program of the Pompeu Fabra University and the Hospital del Mar Medical Research Institute, located in Barcelona. My current research is focused on the development of new computational strategies and tools serving the biomedical research.

What do you like most in your job? 

The most interesting aspect of my job is its multidisciplinary nature. The projects that we develop and the research team that I lead synergically integrate knowledge and professionals from several disciplines, such as medicine, biology, computer sciences, chemistry and pharmacy.

What kind of tasks your job includes?

As director of a program (a kind of academic department), constituted by more than sixty professionals including ten principal investigators and their groups, I have tasks related with the coordination and strategic guidance of the program, including bureaucratic duties that, as you can imagine, are the less attractive. In addition, I have some direct collaborators within the program, and I develop my own research projects in collaboration with them.

What kind of skills your job requires?

My job requires scientific and human experience and I think that have a lot of this taking into account my age.

What do you consider your biggest achievement in your scientific career?

I am particularly proud of the DisGeNET knowledge resource on gene-disease associations that we have been developing along the last ten years. It has become a worldwide recognized resource with more than 5000 users per month and more than 1000 bibliographic citations.

What is the most embarrassing thing you did in the lab while doing experiments?

Since I use to work in silico (computational) labs, explosions are not particularly usual, but we remember incidents related with floods in the room were our computer servers are located, which were particularly damaging.

Which scientist do you admire the most and why?

I particularly appreciate the history of Paul Janssen and his ability for leading an international pharmaceutical company without abandoning his direct involvement in the successful discovery of new drugs.

Which paper of yours you are the proudest of and why?

The papers that we have published about the DisGeNET resource, for instance the last one recently published in Nucleic Acids Research. I am also proud of my paper in Nature Reviews in Drug Discovery in which we reported the results of the IMI eTOX project on data sharing in predictive toxicology.  

Which field of medicinal chemistry do you consider the most promising in the future?

I am probably biased in this respect, but I think that the computational methods and tools offer great opportunities to medicinal chemistry. In particular, the joint exploitation of the biological, chemical and medical big data is very promising for improving the drug discovery process.

What would you like to ask from other medicinal chemists?

I would ask my colleagues to keep them always open-minded, combining their deep experience in the field of their specialization with a global scientific perspective.

What would you guess to be the next major breakthrough in medicinal chemistry?

Given my current professional focus, I do not have a deep insight on all the facets of the medicinal chemistry. However, I think that the incorporation of the systems biology perspective in the design of new drugs offers interesting perspectives.

Where and when did you obtain your PhD diploma?

For the past 4 years I have been working on my PhD at Instituto Superior Técnico, University of Lisbon, Portugal, under the supervision of Prof. M. Matilde Marques, Prof. Rita Guedes and Dr. Luís Sobral. I expect to obtain the degree during this Summer 2020. As part of my PhD project, I also collaborated with Inteligand Company, the University of Vienna and the Fraunhofer Institute.

What is the topic of your PhD project?

My PhD project focuses on epigenetics in cancer. I designed new EZH2 inhibitors, using 3-D pharmacophore models. Following this computational campaign, I selected and synthetized some of the most promising molecules with the intent of testing them against the target. Both biochemical and cellular assays were developed and implemented in order to identify hit compounds. In addition, ADMET profiling of the hits was also performed.

What are your current research interests?

As a Pharmacist, I would like to further build a research career in the development of new medicines. Metabolism and toxicity studies are expertise areas in which I would strive for an opportunity to work on.

What do you consider your biggest achievement in your scientific career?

My scientific career is still young, but I felt particularly rewarded that my computational models actually yielded hit compounds with good activity against my selected target.

Which scientist do you admire the most and why?

It is impossible for me to consider just one scientist. I admire many scientists who I have met during my scientific journey. I had the privilege to have meaningful conversations and learn a lot with people who are passionate about their research. People who work beyond the lab and dedicate their work so others may benefit. People with honest behavior, integrity, resilience and a sense of responsibility. People who give a voice to the aspiring scientists.

I feel mostly inspired by the examples set by women in science. Unfortunately, I feel that nowadays, women researchers still do not get the same attention, as well as credibility, enjoyed by their male counterparts. This cultural issue has been evolving in a positive way, however it is a struggle that we, women, inspired by other scientists who set the tone and example, should keep in mind and use as an extra inspiration in our daily work.

Fortunately, I have had many examples of people who can inspire others and I am grateful to all of them, particularly my supervisors for influencing and shaping the way I look at science, the way I work every single day.

Did you experience any unfair situations during your scientific career?

Unfortunately, there is a lack of opportunities in science in Portugal. I have contacted and felt the frustration in many young talents, who get discouraged and abandon their scientific careers.

Which paper of yours you are the proudest of and why?

At this stage in my career, I would say my next one!

Which field of medicinal chemistry do you consider the most promising in the future?

I consider that medicinal chemistry is trending from therapeutics to diagnosis. Future will focus beyond the therapeutic target discovery and design of new modulators. Diverging from the actual amount of effort in trying to cure certain diseases (which should be always a purpose in medicinal chemistry) or develop new drugs with improved safety or efficacy profiles, I believe that the future of medicinal chemistry will allow us more certain, clear, and well-timed diagnosis of certain diseases, allowing us to prevent them, or at least have a better prognosis for them.

Predictive toxicology of the drugs is one promising field in medicinal chemistry. In a near future we could describe a complete ADMET profile using computational tools and large-scale in vitro models.

Thanks to the disruptive emerging technologies, Medicinal Chemistry will change. Big data, machine learning, artificial intelligence will all be crucial in changing the traditional Medicinal chemistry. The trends in cutting-edge innovation will be transversal to all the Medicinal Chemistry.

As EFMC is celebrating its 50th anniversary - we had the chance to interview Prof. Henk Timmerman, one of the founding father of the European Federation for Medicinal Chemistry, who was recently awarded the title of EFMC Honorary Fellow.

How did you get interested in Medicinal Chemistry?

Long story...I started my “chemistry” study in 1956. The first 4 years, the programme was very broad, but at the end of what we would call the bachelor level now, I bought a book with the title “Chemistry at the Service of Mankind” and was impressed by the stories on penicillin, DDT, crop protection, herbicides; and by the perspectives of compounds with a biological activity in general.

For what is now called master’s degree, I studied under the supervision of Prof. Wijbe Nauta, who was not only a professor at the Vrije University Amsterdam but also research director of the local pharma company Brocades. My future in science was defined!

(I would like to add that the term Medicinal Chemistry was at that time hardly introduced in Europe, and the field was certainly not accepted as an independent discipline yet)

What was the topic of your PhD project?

The title of my PhD thesis was Synthesis 2-Alkyl-1-[ortho-alkyl phenyl]cyclohexanols (Synthesis, conformation and some pharmacological investigations).

It was interesting that I could make use of NMR with one of the first instruments in the country (60 megacycles at that time) and in vitro pharmacology techniques, both not very common at that time.

Can you tell us more about your Career?

In the sixties it was, in The Netherlands at least, not common to start your career with a postdoc position. One went after obtaining the degree straight to a position in research, teaching or similare. I joined the team of Prof. Nauta at Brocades, in the pharmacology department.

Later on, I became the scientific director of the Pharma division of the company Gist Brocades, which was a world leader in antibiotics research.

In 1979 I returned to academia to become the successor of Prof. Nauta. 

As a special effort, I initiated a programme to stimulate the development of pharmaceutical research in Indonesia. This programme became very rewarding when we were able to introduce modern research in the « Fakultas Farmasi in Yogyakarta ». About ten local PhD programmes were completed and by far the most of the PhD's became full professor in Indonesia.

Currently I still serve science (EFMC, Dutch med. chem  section. I am also editor of a scientific journal: DDT-T), serve society (active in the « Dutch Society Against Quackery ») and involve myself in some social aspects.

What were your research interests?

My research has been concentrated on the relationships between structure and activity of biologically active compounds, with the objective to obtain new substances with an attractive profile for using them as active ingredients in medicines, or to become tools in solving existing questions in pharmacological issues (mechanisms of actions, receptor identification, receptor structures, etc.)

As a field I had selected histaminergic ligands, both agonists and antagonists. We were able to contribute to the the knowledge about all four types of histamine receptors; in 1979 only the H1 and the H2 receptor had been identified.

What kind of skills are needed to be a good researcher?

For teaching, it is clear you should be able to transfer knowledge, but moreover - and maybe more importantly - to educate people in a broader sense,  to  stimulate  scientific  curiosity,  to make  sure the  become  'independently' thinking  scientists. For research, a med. chemist needs knowledge in a very broad field and be able to communicate with colleagues in other scientific fields.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

When I was a PhD student, I carried out a hydrogenation experiment. At a given moment the autoclave I used started to leak hydrogen! It made a terrible noise but was also extremely dangerous. The stupid thing was that I did the experiment during evening hours, being the sole person in the lab, inacceptable.

Did you experience any unfair situations during your scientific career?

It was during my years in industry. It happened twice that there was a vacancy for which I was told by management that I was the right person for but went to somebody which was senior. Do you understand? A clear case of mismanagement.

Another one: We had found a series of new ligands, with a very high activity at a given receptor. A co-worker of me told during an unofficial meeting at a department abroad about the finding. To our big surprise, one person attending the meeting filed a patent application on "our" series of compounds, with the activity we had found earlier. My co- worker had been imprudent, the other person involved showed an uncollegial, and even an inacceptable behaviour.

Which field of medicinal chemistry do you consider the most promising in the future?

Without any doubt the further increase of interdisciplinary - I even prefer the term « transdisciplinary ». Those approaches will determine the coming successes of med. chem. research

What would you like to ask from other medicinal chemists?

Please, accept that organic synthetic chemistry, having been for many years the driving force of med. Chem, plays no dominating role in med. Chem anymore. New perspectives come from biology.

And also, please, read the position paper on our discipline!

If you would like to know more about Prof. Timmerman, stay tuned to the YouTube Channel were we will publish the full interview!

Today, our #Iamamedicinalchemist is the most meritorious runner-up of the 2019 EFMC Prize for a Young Medicinal Chemist in Academia.

Where and when did you obtain your PhD diploma?

2008 (ETH Zurich, Switzerland)

What was the topic of your PhD project?

Design and synthesis of inhibitors of the antimalarial target enzyme IspE (Prof. F. Diederich)

Where did you have your postdoc position?

Institut de Science et d’Ingénierie Supramoléculaires, Strasbourg, France (Prof. J.-M-Lehn)

Where do you work at the moment and what is your current position?

Head of department at Helmholtz Institute for Pharmaceutical Research Saarland and full professor at Saarland University, Saarbrücken, Germany

What are your current research interests?

Anti-infective drug discovery using both established and innovative, protein-templated approaches

What do you like most in your job?

The creativity and freedom to focus on the projects that inspire me the most.

The diversity of the activities: research, teaching, project discussions with coworkers and collaboration partners, writing, presenting, attending conferences etc.

What kind of tasks your job includes?

Carry out research, teaching, project discussions with coworkers and collaboration partners, writing scientific papers and grants, presenting the results, attending conferences, serving on committees etc.

What kind of skills your job requires?

Creativity, communication skills, critical thinking, problem-solving skills, organisational skills, time-management skills

What do you consider your biggest achievement in your scientific career?

Obtaining the ERC starting grant and securing my current position

How many PhD and postdoc students do you have at the moment?

13 PhD students and 10 postdocs

Are you currently looking for a new PhD and postdoc students?

Yes always

What are the features of a successful PhD student or postdoc?

Self-motivated, creative, persistent, meticulous, interested to venture into new fields/learn new techniques

How would you describe yourself as a supervisor?

Open-minded, giving coworkers a lot of freedom do develop their own ideas, supportive, ambitious, creating and maintaining a collaborative environment and spirit in the group

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

As a Master’s student, I handled 1,2-ethane-dithiol for the first time and was not aware of its smell.

Which scientist do you admire the most and why?

Marie Curie for her scientific achievements and for being an important role model as a female scientist, certainly ahead of her time.

Which paper of yours you are the proudest of and why?

First report on the synergistic combination of dynamic combinatorial chemistry and structure-based de novo design (M. Mondal et al., Angewandte Chemie, 2014)

Which field of medicinal chemistry do you consider the most promising in the future?

As an academia, I believe it is most valuable, rewarding and urgent to work in a field that is underexplored/neglected by the pharmaceutical industry such as anti-infective drug discovery.

What would you guess to be the next major breakthrough in medicinal chemistry?

1. Obtaining structures of complexes of target protein and inhibitor on a routine basis thanks to the continuous developments in structural biology, in particular electron microscopy.
2. Cell-based target validation thanks to progress in the field of chemical probe design.

Today, our #Iamamedicinalchemist is the winner of the 2019 EFMC Prize for a Young Medicinal Chemist in Industry.

Discover her full-story below!

How did you get interested in Medicinal Chemistry?

Medicinal chemistry is the start of an incredibly long and complex story about getting a drug to the patient.  I find being involved at the ‘birth’ of the project and being able to influence and impact how this molecule is made from such an early stage, whilst always keeping an eye on maintaining flexibility and optionality for future production scale, to be fascinating role.

Where and when did you obtain your PhD diploma?

In 2007 – it was a joint program between Vienna University of Technology and University of Chemistry and Technology in Prague.

What was the topic of your PhD project?

Asymmetric Baeyer-Villiger Oxidations using 2^nd Generation Biocatalysts.

Where did you have your postdoc position?

1^st York Structural Biology Laboratory, University of York, UK as Erwin-Schrödinger Fellow

2^nd Dept. of Biotechnology and Enzyme Catalysis, Greifswald University, Germany

Where do you work at the moment and what is your current position?

Novartis Institute for Biomedicinal Research, as a group leader focused on driving progress and adoption of biocatalysis across the entire portfolio and at all stages in a compounds evolution.

What are your current research interests?

Biocatalysis is a subject that I believe has huge value for the synthesis of complex molecules, complementing traditional organic chemistry and providing a way for the pharma (and broader chemical industry) to change their image to one of an industry focused on sustainability and positive environmental impact.  My research interests revolve around finding game changing biocatalysis solutions for the production of API’s, which we achieve through application of existing technologies and a constant drive to expand and develop the science though techniques such as  protein engineering and bio-conjugations.

What do you like most in your job?

I find the scientific creativity and constant innovation to be very satisfying.  Looking at a route and working with synthetic teams to reimagine what’s possible creates an energy and motivation to succeed that is addictive!  There is a strong angle on people development in my role that occurs when people engage with biocatalysis and want to learn more and participate in what is naturally a very multi-disiplinary science, operating across a very wide research area.

What kind of tasks your job includes?

Discovery and implementation of novel and established biocatalysis technologies into drug discovery/development, which of course results in the ultimate goal of offering access to late-stage functionalisation capabilities, and the ability to support the drug development process in many tangential ways, such as the synthesis of metabolites. As a group leader, I have line management and various leadership roles, which broaden my role into many other aspects of the Novartis business, into areas as diverse as leading the promotion team, evaluating ‘strategic joint ventures with academic/industrial counterparts and leading a team of people to develop transformational science.

What kind of skills your job requires?

You need to love what you do – as in any field of science the progress is rapid and so staying on top of that becomes a lifestyle rather than a ‘job’!  Following the literature, building networks and relationships and constantly looking for opportunities to apply the science is key.  Equally being realistic and knowing the limitations of what is possible is key to maintaining credibility :)

Additionally, my job involves dealing with people from many disciplines and backgrounds at various levels in their career, so empathy, an open mind and good listening and communication skills are all vital (maybe a good dose of patience as well)!

What do you consider your biggest achievement in your scientific career?

Outside of being selected for this prize, which I view as an amazing honour, last year our team created a proposal for, and won a “Genesis Labs” award.  This is a global competition for independent scientific pursuit, sponsored by Novartis, with the goal of delivering transformational science. We are currently half way through the project, in a very exciting phase.

How many PhD and postdoc students do you have at the moment?

Within my group are many highly experienced researchers who have attained academic excellence at different levels from apprentice to multiple post-docs, and who continue to grow their knowledge and capabilities on a daily basis, solving problems which directly impact the value of the Novartis portfolio.  Outside of Novartis I lead a number of academic collaborations, including cooperations with PhD and postdoc students, as well as undergraduate lab courses in the local university.

What are the features of a successful PhD student or postdoc?

What separates a good from a great student is someone who has developed the confidence in their abilities to conduct independent research but maintains a critical internal ‘review process’ so they know when to keep pushing through a challenge or realise a topic is no longer worth pursuing.  Being enthusiastic, a good communicator, resilient and supportive of others are all features that make a researcher, at any level, successful in their field.  People who understand the impact and purpose of their research always seem to find the ability to ‘keep pushing through’ much better than those who are less involved in the bigger picture of what they are contributing towards.

How would you describe yourself as a supervisor? 

I would like to think my team finds me to be the person they can come to when they have a problem, a success or a question.  I prioritise finding time to listen to my team, understand their objective/motivation and finding ways to support them as they develop personally and professionally. Seeing people achieve what they thought was impossible, deliver excellence and enjoying their job is what makes me the happiest.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

I think as a researcher, we all have a little bit of a ‘cowboy’ in us and sometimes the drive to get things done quickly overcomes our more rational selves.. leading most people to have had a least a little drama in the lab – I created a little excitement one morning when washing out unreacted sodium from a Birch reactions into the sink...

I also seem to be on a bit of a roll currently with embarrassing acts outside the lab involving pouring coffee over myself, or my boss, or his boss... I don’t think I’m clumsy, but sometimes I gesticulate a little too much with my hands...

Which scientist do you admire the most and why?

Prof. Uwe Bornscheuer! My postdoc boss, he is a wonderful and kind person, 1^st class scientist and has a great sense of humor!

Did you experience any unfair situations during your scientific career?

On being awarded a postdoc fellowship, I was told by several of my peers that I had won it only because I am woman.

That had a huge impact on me, as until that point I only considered my competition to be better scientists, and progression or recognition being awarded solely on that basis.  When I heard comments around my fellowship being awarded on the basis of political or optical reasons, I found it very unfair.  Taking a step back from this, when listening to feedback from the grant agency about the exceptional quality of my scientific proposal and knowing the effort I put in during the two months time  it took to write it, I was able to disconnect myself from comments which I attribute to ‘sour grapes’ and an outdated mentality. There will always be situations that can be interpreted as being unfair, I only hope it’s not me causing it or that I have the strength of character to get past it.

Which paper of yours you are the proudest of and why?

The one I’m currently writing – a tutorial review.  Being able to bring together a whole subjects worth of science in a comprehensive and easily accessible manner, building interest in the topic and sharing my enthusiasm for it is a great reward for the pain of summarising and coherently bringing together 1’000’s of papers and decades of research!!

Which field of medicinal chemistry do you consider the most promising in the future?

Medicinal chemistry is the start of the drug development process – it is a wonderfully multidisciplinary field of science and needs to solve many problems.  I am always keen and motivated to find ways to leverage the work and results generated by medicinal chemistry teams in later stage development and finding technologies that are as applicable to the development chemist, as they are the medicinal chemist, builds in a layer of efficiency and effectiveness that streamlines the drugs development and production.  Anything that supports this broadly applicable and scalable technology creation and adoption is going to deliver meaningful results in any organisation.

What would you like to ask from other medicinal chemists?

As a medicinal chemist you have the pressure to deliver to sometimes near impossible timelines, but please take a chance sometime to try biocatalysis and see what it can do for you and your project!  You won’t be disappointed :)

What would you guess to be the next major breakthrough in medicinal chemistry?

Utilising the advances we have made in understanding topics such as protein folding and SAR I see the future of rationale based drug design being very bright.

Today, our #Iamamedicinalchemist is Dmitry Mazunin from F. Hoffmann-La Roche in Basel, Switzerland.

Discover his full-story below!

Where and when did you obtain your PhD diploma?

I did my PhD with Prof. Jeffrey W. Bode at ETH Zurich from 2011-2016

What was the topic of your PhD project?

Initially I worked on bullvaene, a shape-shifting molecule. However, my doctoral thesis deals with recently discovered KAT ligation and its use as a bioorthogonal reaction.  We have used KAT ligation for hydrogel formation and functionalization.

Where did you have your postdoc position?

For my postdoc I moved to LMB in Cambridge, UK supported by SNF fellowship. I spent 18 months in the group of Prof. Jason W. Chin working in the area  of chemical biology.

Where do you work at the moment and what is your current position?

Currently I am working as a medicinal chemist at F. Hoffmann-La Roche in Basel

What are your current research interests?

Our medicinal chemistry department  is supporting preclinical reseach in terapeutic  areas such neuroscience, oncology, inflammation, immunology and infectious desease. Currently I am a part of oncology section and  involved in design and synthesis of our target copounds ranging from lead identification to lead optimisation.

What do you consider your biggest achievement in your scientific carrier?

Personally I would consider a big (biggest) achievment in my carrier if I could contribute to a development of a drug, which will help patients. Until today it has been an educational and adventurous  scientific journey from my chemistry studies over PhD and Postdoc to my current position.

How many PhD and postdoc students do you have at the moment? Are you currently looking for a new PhD and postdoc students?

At the moment medchem department  does’t host any PhDs or Postdocs. Recently we had a 3-months stay of a PhD student from Germany.  However, MedChem department at Roche in Basel has been organizing a one-year intership program (RICH) for students for many years.

How would you describe yourself as a supervisor?

I try to be collegial and teach my students to work independently without a fear to fail. Till today I have been fortuate to supervise six students and all of them started or are planning to start their PhD. At least I haven’t scared anyone.

What is the most embarrassing thing you did in the lab while doing experiments?

As all students I had few small run-aways and one a bit bigger while trying to scape up a synthesis. Fortunately I have never had an explosion, but was present in the lab when two happened and it is not fun at all. One of them happened for water splitting where you generate oxygen and hydrogen. It was done on larger scale and two gases were collected in two barrels with safety detectors. However, the setup was drawn by a chemist, but the apparatus was build by electricians . And here a funny part starts: for chemist a kathode is a plus, and anode is a minus; for a electrician visa versa.  Electriacians connected the setup not in the right way. The gases were collected in wrong barrels and the safety detectors didn’t help when one of them was leaking. After certain time when the ratio was 2:1 it exploded.

Which field of medicinal chemistry do you consider the most promising in the future?

Oncology would remain unfortunately one of the biggest challenges for biology but also for drug discovery.

Today, our #Iamamedicinalchemist is Dr Giannamaria Annunziato from the Università degli Studi di Parma, Italy.

Where and when did you obtain your PhD diploma?

I obtained the Ph.D. diploma in March 2017 at the University of Parma, spending four months at ETH of Zurich as visiting Ph.D. student.

What was the topic of your PhD project?

“New strategies to eradicate Microbial Resistance”, I’ve been involved into a very challenging and exciting project, from the synthesis of small molecules as inhibitors of pathogens’ “non-essential” pathways to the total synthesis of natural products derivatives endowed with antimicrobial activity.

Where did you have your postdoc position?

I had a postdoc position as a Medicinal Chemist at the University of Parma.

Where do you work at the moment and what is your current position?

At the moment I am Assistant Professor of Medicinal Chemistry at the Department of Food and Drug of the University of Parma and also, I am the representative of Medicinal Chemistry under-35 years old scientists at the Italian Chemical Society (Società di Chimica Italiana, SCI Giovani).

What are your current research interests?

Now I have the opportunity to work on different topics; I am still working on my former PhD project, trying to find small molecules as adjuvants of already existing antibiotics for which pathogens have developed resistance. From my point of view this is a very promising approach in this field because these targets that are “non-essential” are less prone to mutate and their inhibition make bacteria more susceptible to the attack of the host immune system and antibiotics. Another project in which I am involved is focused on the development of pharmacological chaperones able to restore the physiological activities of a mutated proteins underlying human diseases and, finally, I am also working on natural extracts in order to identify natural compounds endowed with interesting nutraceutical activities.

How would you describe yourself as a supervisor?

I always try to make my students curious about their work, pushing them to be patient, motivated, hard-working and creative which I think are the most important skills in this work. 

Which scientist do you admire the most and why?

Rita Levi Montalcini, the first and only (up to now) Italian woman which won the Nobel prize in Medicine and Physiology. In my opinion she has been one of the most important Italian scientists, and I appreciate her commitment in science but also in social problems at a time when women hardly have chances.

Did you experience any unfair situations during your scientific career?

Fortunately, no

Which paper of yours you are the proudest of and why?

I am proud of every single paper I have contributed to publish in a scientific journal, there is a lot of studies and work behind all of them. Anyway, up to now, the paper for which I am proudest is my first as corresponding author, on the discovery of a new class of antifungal agents that selectively inhibits microbial carbonic anhydrase. Journal of Enzyme Inhibition and Medicinal Chemistry; 2018, 1, 1537-1544. 

Which field of medicinal chemistry do you consider the most promising in the future?

The concept of pharmacological chaperone therapy has been emerging in the last years and is very intriguing and interesting. Pharmacological chaperones are small molecules that bind into a target protein and stabilize its native structure helping mutated proteins to restore their biological function. The ability to restore the native physiological function of a protein trough a small molecule or bio-macromolecule is something really exciting and challenging to obtain. Such modulators can find large applications in misfolding human diseases, such as neurodegenerative diseases, so I think that they will play an increasingly important role in the medicinal chemistry field in the next decades.

This week's #Iamamedicinalchemit is Michele Mari from the University of Urbino “Carlo Bo” Italy. He is also the president of small spin-off company from the same university (GLUOS). Would you also like to have your own company?

Where and when did you obtain your PhD diploma?

I obtained my Ph.D. at University of Urbino “Carlo Bo” Italy, spending 9 months also at ETH Zurich as visiting Ph.D. Student

What was the topic of your PhD project?

“Strategic indole functionalization for the synthesis of tryptophan containing alkaloids and biologically active tryptamines”, I’ve been into pretty much chemistry from total synthesis of natural products to new anticancer compounds.

Where did you have your postdoc position?

I have a postdoc position in the same University; I love to work in a quiet place like Urbino, surrounded by the beauty of an UNESCO site.

Where do you work at the moment and what is your current position?

At the moment I share my worktime between my postdoc position at University of Urbino and my start up company GLUOS (university spin off).

What are your current research interests?

We are working on a lot of things at the moment, I’m trying to push forward the pioneering work that our group did on melatonin receptors ligands, we are synthesizing some interesting natural products with antibiotic activity, another thing that we are always looking for is the development of novel antioxidant agents, finally I am also working on the analysis and biological activity of different natural extracts.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

It happened that when we were quenching some old reagents a one meter high green flame came out from the flask, but we were working safely so it was not a problem to manage it and dispose everything in the right manner to the waste.

Which scientist do you admire the most and why?

I cant talk for hours about this because I really consider myself a science nerd, and I love to follow also other people’s work, for sure a scientist that I really like is Prof. Paul Wender, with his reaserch that goes from chemistry to biology and medicine, I’m really passionate in particular in Organic Synthesis because I’m more a synthetic medicinal chemist, so I really like also the work of Prof. Phil Baran and Prof. Erick Carreira. I have to say that there are scientists I’ve been working with that really inspired me and I have them as models such as Prof. Jeffrey Bode and Prof. Giovanni Piersanti. Than I have to say Giulio Natta, our only Italian Nobel Prize in Chemistry and last but not least Prof. Robert Woodward that gave a touch of artistry to organic synthesis.

Which paper of yours you are the proudest of and why?

Every paper has a story and there’s so much work behind that you must be proud of everything you did. At the beginning it is not so easy to publish and you push a lot to reach the goal, so for sure my first paper has been quite hard work. Anyway, just have a look to my profile on google scholar and check out, there’s some pretty nice stuff that I’m proud of:
https://scholar.google.it/citations?user=x-zUbsIAAAAJ&hl=it

Which field of medicinal chemistry do you consider the most promising in the future?

I think that cancer is still the greatest problem of our era, we must improve the weapons we have against it, another emerging and urgent problem is improving our antibiotics pull to fight infections and bacterial resistance. So I would say that these two still remain the challenges to face in the future.

This week's #Iamamedicinalchemist is Jorge Peiró Cadahía from the Scandinavian biopharmaceutical company Nuevolution A/S, Copenhagen, Denmark.

Are you motivated to do synthesis because the difficult compound you are synthesizing might be "the one" which turns into a useful drug? Or do you have other great reasons to do synthesis?

How did you get interested in Medicinal Chemistry?

During my B.Sc. studies in 2012 I had the great opportunity to carry out a research project in the group of Prof. Adoración Gómez Quiroga at the Universidad Autónoma de Madrid. The project was based on the synthesis and biological evaluation of Pt-complexes with anti-tumoral properties. This bio-inorganic research project was my first contact with Medicinal Chemistry and encouraged me to start my M.Sc. on Organic and Medicinal Chemistry at the Technical University of Denmark.

Where and when did you obtain your PhD diploma?

I have obtained my Ph.D. in December 2017 from the Technical University of Denmark, Copenhagen, DK. A six-month research stay in the group of Prof. Matthew Gaunt at the University of Cambridge, Cambridge, UK, was part of the degree.

What was the topic of your PhD project?

The main project of my Ph.D. focused on the synthesis and biological evaluation of reactive oxygen species sensitive prodrugs for the treatment of chronic inflammatory diseases like e.g. rheumatoid arthritis. A smaller sub-project carried out was based on the development of novel Pd-catalyzed carbonylation reactions.

Where do you work at the moment and what is your current position?

I am a Research Scientist at the Scandinavian biopharmaceutical company Nuevolution A/S, Copenhagen, DK (www.nuevolution.com).

What are your current research interests?

Our current research interest is the development of novel tablet-based drug therapies for human diseases within oncology and chronic inflammation. Examples of such autoimmune inflammatory diseases are multiple sclerosis, rheumatoid arthritis, psoriasis, inflamed fatty liver and chronic inflamed colon or intestine, where significant unmet medical need remains.

What do you like most in your job?

The fact that a specific compound you have synthesized in the lab, although sometimes very synthetically challenging, can be potentially “the one” that will create a better treatment or even a cure to very serious diseases motivates not only my daily work but probably also of many medicinal chemists.

What kind of tasks your job includes?

Design and synthesis of new analogues in “hit-to-lead” and “lead-optimization” programs as well as evaluation of biological results.

What kind of skills your job requires?

Strong synthetic Organic Chemistry knowledge as well as Medicinal Chemistry know-how.

What do you consider your biggest achievement in your scientific career?

My first publication “Synthesis and evaluation of hydrogen peroxide sensitive prodrugs of methotrexate and aminopterin for the treatment of rheumatoid arthritis. J. Peiró Cadahía, J. Bondebjerg, C.A. Hansen, V. Previtali, A.E. Hansen, T.L. Andresen, M.H. Clausen. Journal of Medicinal Chemistry 2018, 61 (8), 3503-3515 (https://doi.org/10.1021/acs.jmedchem.7b01775)” was probably the first big achievement in my scientific career. But to be chosen by the Danish Society for Medicinal Chemistry and Chemical Biology (DSMKB) as the Denmark’s nominee for European Champion in Medicinal Chemistry at the EFMC-YMCS 2018 was probably the biggest achievement so far. It was an honor for me to be given the opportunity to present my work in a truly international and relevant Medicinal Chemistry conference as the EFMC-YMCS is.

What are the features of a successful PhD student or postdoc?

Patient, motivated, hard-working, innovative and creative are probably the most important skills to become a successful Ph.D. student.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

Probably forgetting to turn off the vacuum when filtering Pd/C letting it to dry and get red-hot or quenching LAH with septum on the flask, producing a small explosion. You sometimes learn from mistakes.

Which scientist do you admire the most and why?

I do not dare mentioning a single and particular scientist without first expressing my admiration to all those scientists who despite the great difficulties in finding financial support for their research they persist and fight every day to continue running their groups. With all the above mentioned, I really admire Nobel Laureates Heck, Negishi and Suzuki for their contributions into the field of palladium-catalyzed cross couplings in organic synthesis.

Did you experience any unfair situations during your scientific career?

If any, luckily not of great importance.

Which paper of yours you are the proudest of and why?

I am proud of every single paper I have contributed to publish in any scientific journal and the humble list is shown below:

- Synthesis and evaluation of hydrogen peroxide sensitive prodrugs of methotrexate and aminopterin for the treatment of rheumatoid arthritis. J. Peiró Cadahía, J. Bondebjerg, C.A. Hansen, V. Previtali, A.E. Hansen, T.L. Andresen, M.H. Clausen. Journal of Medicinal Chemistry 2018, 61 (8), 3503-3515 (https://doi.org/10.1021/acs.jmedchem.7b01775).

- Methotrexate prodrugs sensitive to reactive oxygen species for the improved treatment of rheumatoid arthritis. N.S.Andersen, J. Peiró Cadahía, V. Previtali, J. Bondebjerg, C.A. Hansen, A.E. Hansen, T.L. Andresen, M.H. Clausen. European Journal of Medicinal Chemistry 2018, 156, 738-746 (https://doi.org/10.1016/j.ejmech.2018.07.045)

- Diastereoselective C–H carbonylative annulation of aliphatic amines: a rapid route to functionalized γ-lactams. Z.M. Png, J.R. Cabrera-Pardo, J. Peiró Cadahía and M.J. Gaunt. Chemical Science 2018. (https://doi.org/10.1039/c8sc02855a)

Which field of medicinal chemistry do you consider the most promising in the future?

I believe PROteolysis-TArgeting Chimeras (PROTACs) are very promising small molecule targeted therapy strategies which many big pharma and biotech companies have relatively recently gotten onboard for its potential. I am sure we will soon read the first published clinical trials and hopefully also the first marketed PROTACs.

Christina Lamers from the University of Basel is this week's #Iamamedicinalchemist! Read below if she ever forgot anything important when doing a dilution series.

Would you also like to take part in our interviews? Send us a message and we will send you the questions. After answering them we will share your story with our followers!

How did you get interested in Medicinal Chemistry?
Before I became interested in specifically Medicinal Chemistry, my passion and interest for Chemistry was evoked by my Chemistry teacher in high school. He explained to me that every reaction, even in our body, is following the same basic rules of attraction, repulsion and reactivity and if you understood those rules you could explain and design such reactions. It was always clear to me that I want to use this knowledge to create something useful, but not like new materials such as plastics. And since I was also quite interested in human anatomy, physiology and pathophysiology, I chose to study pharmacy, where I found all these topics combined. From the very first day at university, it
was clear to me that I was going to get a PhD and continue working in science, with Pharmacy as a backup plan. Seeing every process in the human body as a chemical interaction fascinates me, especially because you can modify these reactions with a designed molecule, for example binding to a receptor might be competitive to endogenous ligands. As soon as you understand the molecular interaction, you can modulate it to treat diseases. Therefore, I started my PhD in Medicinal Chemistry immediately after completing my Pharmacy studies, and worked on small molecules activating nuclear receptors.

Where and when did you obtain your PhD diploma?
I did my PhD in the group of Prof. Manfred Schubert-Zsilavecz at Goethe University in Frankfurt am Main, Germany. I also studied at that university and had the chance to check out all the working groups before choosing one with a topic and methods I liked the most. After nearly five years of PhD research, I obtained my PhD diploma in December 2014.

What was the topic of your PhD project?
My main PhD projects were the synthesis and characterization of small molecules to modulate the nuclear receptors FXR and PPARs, which are involved in several metabolic regulations like fatty acid and glucose homeostasis. Our molecules had similar structural features to the endogenous ligands, namely an acidic head group and a lipophilic tail... which didn’t make it too easy for purification and solubility

But isn’t it stunning that molecules like fatty acids, which used to be considered a nutritional factor are actually signaling molecules?

I was also involved in the cellular testing of several nuclear receptor modulators in our transactivation assay systems, and I was quite happy to also learn cell culture and other in vitro assays. I think this is very important for a medicinal chemist to also understand the in vitro systems that are used to judge their liability and comparability, especially if you want to create a sound SAR.

Where did you have your postdoc position?
For my first postdoc, I completely changed direction and went into the chemical biology lab of Prof. Christian Heinis at EPFL, Lausanne, Switzerland with a Marie Curie Individual Fellowship. I wanted to learn a more sophisticated and faster way to identify a lead compound than the trial-and-error method of a systematic SAR investigation. With Phage Display, you basically start the other way around and have a huge library of 10 9 compounds from which you let the target select the most appropriate ones. Obviously, you are restricted to peptides as your scaffold, but in the Heinis lab we are actually able to chemically modify our peptides to lead to new and pre-constrained molecular formats.
These modified peptides have a high affinity, and are specific and able to bind difficult targets like protein-protein interactions.

Where do you work at the moment and what is your current position?
In November of last year, I moved to Basel, and I am now working in the group of Prof. Daniel Ricklin in the pharmaceutical department of the University Basel as a postdoc.

What are your current research interests?
I am still working on peptides as possible therapeutics, which of course is a challenging task seeing their limitations especially in pharmacokinetic parameters. But our group in Basel is targeting the complement system, which is circulating in blood, already circumventing the limitation of no cell permeability. The topic especially fascinates me because in recent years I realized how underestimated the innate immune system is. This is anyway a summarization of several different intra- and extracellular mechanisms of host defense and its involvement in different diseases is getting clearer and clearer. Using our
tools to study these mechanisms will help us understand their involvement in age related and autoimmune diseases, which are pressing health issues now and even more in our future.

What do you like most in your job?
I really love doing reactions, creating a new molecule and testing the compound
afterwards, especially when you realize you have created something very active. The lab work is always fun for me, especially if you can solve a problem in a creative way.

What kind of tasks your job includes?
My job includes peptide synthesis, purification and the analytic evaluation as well as the testing in SPR and other assays. In addition, I am supervising students and teach a class of quantitative analytics for pharmaceutical students.

What kind of skills your job requires?
Organizational and planning skills, time management, creativity is a plus, analytical skills, communication and presenting skills, networking skills are helpful to establish new collaborations.

What do you consider your biggest achievement in your scientific career?
Winning the Marie Curie Fellowship is for sure my highlight so far, but I hope big achievements are still ahead of me

What are the features of a successful PhD student or postdoc?
In my opinion the most important feature is endurance and commitment to your project. In my experience, most experiments don’t work the first few times and you have to try several approaches. You still need to motivate yourself to keep trying even if you had weeks of disappointing results. And to become an excellent PhD you need to be curious. Not accepting results as given but always ask for the why and how will lead to new observations and might be the start to a new groundbreaking project.

How would you describe yourself as a supervisor?
When I was in my PhD I appreciated very much freedom in my research. I believe that you learn more when you figure out problems on your own and make your own mistakes. So as a supervisor, I always have an open ear if there are problems and my students need advice, but I try to not interfere with their planning and analysis of projects to leave them as much freedom as possible.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
The actual most embarrassing was to realize after measuring a dilution series of 40 samples that I had forgotten to put the stock solution into the first dilution before diluting the rest. So, I had 40 blank samples...

Which scientist do you admire the most and why?
Besides Leonardo Da Vinci, who was a real genius in so many disciplines and so ahead of his time, I really admire Christiane Nüsslein-Volhard not “just” because she became a female scientist in male dominated natural sciences nor because she won the Nobel price (which is pretty awesome), but she is very inspiring! Especially because she doesn’t seem to be able to satisfy her curiosity and still keeps on doing research. I hope for myself that I will also still have the hunger for science when I am supposed to retire

Which paper of yours you are the proudest of and why?
I am the proudest of my paper of the first in class dual FXR antagonist and TGR5 agonist paper from my PhD project because it was a project with a difficult start and it didn’t at all go in the direction we expected. But I kept on working on it and in the end, I succeeded with a nice SAR and story. I pushed to publish and finished the manuscript after I was already graduated so that I really feel this paper is my own baby.

Which field of medicinal chemistry do you consider the most promising in the future?
I expect that the artificial intelligence will become more and more powerful as a tool for medicinal chemists by helping us to use the vast amount of information to come up with new ideas. But I think an experienced medicinal chemist is still needed to actually conduct the successful SAR. On the other hand, I see growing interest in molecular formats adapted from biomolecules like peptides or carbohydrates. Though they don’t show great pharmacokinetic features per se, I think they are able to bind to targets small molecules are not suitable for. And topic-wise, I think the innate immune system is highly under estimated and I expect it to be in some autoimmune diseases the missing puzzle piece for
understanding disease pathology.

What would you like to ask from other medicinal chemists?
I think we need a discussion about publishing and impact factor and how we can make a more transparent and fair reviewing process. Sometimes it feels like an established author name is worth more than solid scientific work. And also, negative reports are valuable and should be published. It is one of the most abundant knowledge on how not to do things but yet nowadays everyone has to figure out by themselves again.

This week's #Iamamedicinalchemist is Cassandra Lee Fleming, a Marie Curie postdoctoral fellow at the University of Gothenburg (Sweden). She is the Winner of the young medicinal chemist meeting in Sweden.

How did you get interested in Medicinal Chemistry?

I have always been interested in understanding how the body works. This in combination with my enthusiasm for a range of science subjects offered throughout my education led me to pursue my research interests within medicinal chemistry field.

Where and when did you obtain your PhD diploma?

I completed my PhD in 2015 at Deakin University (Australia) under the guidance of Associate Professor Frederick Pfeffer.

What was the topic of your PhD project?

In efforts to further develop our understanding of how histone deacetylase (HDAC) inhibitors act at cellular level, my doctoral studies focused on the design and synthesis of fluorescent HDAC inhibitors as tools for cellular imaging applications.

Where did you have your postdoc position?

Following my doctorate, I joined the group of Professor Joakim Andréasson as a postdoctoral researcher at Chalmers University of Technology, Sweden.

Where do you work at the moment and what is your current position?

I am currently a Marie Curie postdoctoral fellow at the University of Gothenburg (Sweden), in the group of Professor Morten Grøtli.

What are your current research interests?

My research interests are centred around the utilisation of light as an external stimulus to control the pharmacological activity of small bioactive molecules in diseased cells and tissues to provide valuable insight into the underlying molecular events of complex disease states.

What do you like most in your job?

I like being able to combine the practical aspects of organic chemistry with problem solving to address the research question at hand. I really enjoy the interdisciplinary nature of my current project and the fact that no two days are ever the same. You are constantly learning new things (even if most of the time this is a result of experiments that just didn’t work!).

What kind of tasks your job includes?

I spend most of my time synthesising fluorescent and light-responsive bioactive molecules and evaluating their photophysical and biological properties. However, more recently, I have also begun to dabble in a bit of multiphoton microscopy.

What kind of skills your job requires?

Curiosity, determination, to be able to embrace failure and to ‘think outside the box’.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?

During my PhD I once accidently flooded the fume hood with water and oil after the hosing on my reflux condenser split and the water ended up flowing into the oil bath. Luckily this happened over the lunch break so not a lot of damage was done, however it did take a while to clean up!

Which scientist do you admire the most and why?

This is a tough question as there are so many inspirational scientists both past and present. However, I really admire Sir Martyn Poliakoff for his science outreach and education work. He communicates a diverse range of scientific topics in a unique and engaging way. He shares his passion for learning with the public and inspires the next generation of scientists — he is an excellent role model for young researchers.

What would you guess to be the next major breakthrough in medicinal chemistry?

I hope to see a significant advancement in our understanding of the underlying molecular events of neurodegenerative disorders (such as Alzheimer’s) so that effective treatments for disease states can be developed.

This week's #Iamamedicinalchemist is Ana Sofia Newton from Yale University. She enjoys working in a creative environment. Do you think drug design requires creativity?

Find her on Twitter! @AnaSofiaNewton

How did you get interested in Medicinal Chemistry?
I had an interest in Chemistry very early on. I did my undergrad studies at the Faculty of Science in Lisbon. At the time Martinho Simões, a distinguished Physical Chemistry Professor, and Amélia Pilar Rauter a pioneer in Carbohydrate Chemistry had a profound impact on me and my initial directions in research. I became more and more interested in Medicinal Chemistry and decided to do my graduate studies at the Faculty of Pharmacy and develop my knowledge in both Medicinal and Computational Chemistry under the supervision of Prof. Rui Moreira and Prof. Rita Guedes.

Where and when did you obtain your PhD diploma? What was the topic of your PhD project?
I obtained my PhD diploma at the University of Lisbon in 2013. “Design, Synthesis, and Evaluation of Peptidyl Inhibitors for Clan CA and Clan CD Cysteine Proteases.” A big title but basically I applied Medicinal and Computational skills for the development of anti-malaria and anti-neurodegenerative agents. It was pretty exciting and I learned tons.

Where did you have your postdoc position?
My interest in drug discovery and Medicinal Chemistry assisted by computer aided-methods lead me to William Jorgensen’s lab at Yale University. Throughout my doctoral and postdoctoral work, I was particularly interested in being able to apply both computational chemistry and organic synthesis in drug discovery. I knew that applying computational strategies to design small molecule inhibitors was important, but at the same time having a strong synthetic background would allow me to rapidly distinguish computational hits that could be feasibly synthesized from those that would represent a substantial synthetic challenge.

Where do you work at the moment and what is your current position? What are your current research interests?
Currently I work at Yale University as an Associate Research Scientist where I am leading two collaborative research projects to design potent, safe, easily administrated, and long-acting small molecule inhibitors that could reduce or eliminate blood cancer growth and skin cancer. The approach combines state-of-the-art technology for molecular design, synthetic organic chemistry, biological assaying, and crystallographic determination of structures of the designed molecules bound to their protein target.

What do you like most in your job? What kind of tasks and skills your job includes?’
I would say being surrounded by people with a lot of creativity. Also, attention to detail and enormous passion for drug discovery are good skills to have if you want to be a good scientist. Perseverance, working as a group and always pushing the projects forward because you will most likely find a breakthrough.

How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
We have 3 PhD students and 4 Postdocs. Currently we have two Medicinal Chemistry Postdoctoral positions open. They will work in close collaboration with experts in computer-aided drug design, biological assays, and protein crystallography.

What are the features of a successful PhD student or postdoc?
Strong organic and medicinal chemistry bench skills, good interpersonal skills, flexibility, and the ability to work well within an interdisciplinary team environment.

Which scientist do you admire the most and why?
I suspect the expected answer would be Sir Isaac Newton. The brilliant British mathematician and physicist is definitely among my top choices. For Newton, all there was in the world was matter moving. His equations are so effective we still use them today. However, Albert Einstein proved that time and space are shaped by matter. He could take a hard, physical problem and boil it down to a powerful visual image, a thought experiment. A creativity process that very few are able to achieve.

This week's #Iamamedicinalchemist is Davide Benedetto Tiz from the faculty of Pharmacy in Ljubljana (Slovenia). Do you agree with him that luck plays a role in synthetic chemistry?

How did you get interested in Medicinal Chemistry?
During the high school I had classes about natural science (biology, geography and chemistry). My professor was so interested about chemistry that transmitted his passion to me. I liked the pathos behind each experiments and the fascination that could stem from putting together small entities such as atoms in order to form bigger substances.
Later, during my master degree, I really fell in love with organic chemistry subjects combined with the pharmacology: this cocktail led me to become a medicinal chemist, a passionate scientist that transfers his synthetic skills into the development of new drugs.

Where and when did you obtain your PhD diploma?
I am currently in my third year of doctoral studies at the faculty of Pharmacy in Ljubljana (Slovenia)

What was the topic of your PhD project?
The topic of my PhD project is the design, synthesis and evaluation of novel DNA gyrase and topoisomerase IV inhibitors. DNA gyrase is a bacterial topoisomerases that catalyse changes in DNA topology and are validated targets for antibacterial drug discovery.
DNA gyrase is primarily involved in the negative supercoiling of DNA during replication, while topoisomerase IV is deputed to the decatenation of the two daughter chromosomes after replication.
From the crystal structure of E. coli DNA gyrase B in complex with a previously developed inhibitor recently disclosed by our research group, I developed further inhibitors which displayed good inhibitory activities against E. coli and S.aureus gyrase B. Some compounds possessed activity against selected Gram-positive bacteria.

Where did you have your postdoc position?
Currently I do not have any postdoc position

Where do you work at the moment and what is your current position?
I currently work at the faculty of Pharmacy in Ljubljana and I carry out my research work as a PhD student in my third year of studies.

What are your current research interests?
My interests are mainly organic chemistry and medicinal chemistry. In particular I am involved in the preparation of carboxylic acid bioisosteres, replacements that are meant to boost the penetration of small-molecules into bacteria. The limited drug entry in bacteria is today one of the limiting factor to develop successful antibiotics.

What do you like most in your job?
Mostly synthesis and purification of compounds. I also perform docking studies of my molecules and other computational studies such as the prediction physicochemical properties. 
Examining the analytical data of a certain compound is also an aspect I like because I feel like solving a riddle and revealing the true identity of a compound is something that makes me satisfied.

What kind of tasks your job includes?
My daily routine includes the preparation of the designed inhibitors, their purification using several techniques (e.g., chromatography and crystallization) and the sample preparation for the collection of the analytical data (NMR, infrared, polarimetry, mass spectrometry and melting point). The most interesting part and sometimes the most difficult is the design of the synthetic route because you have to take into account the compatibility of different groups in a molecule.
Additionally, I am writing review and research papers related to the field of antibacterial discovery.

What kind of skills your job requires?
Patience, I would say, is one of the most important skills because it often happens to deal with failed experiments. Another skill is the manual work since I need to set up the reaction environment and to dose liquids carefully every day. Last, but not the least, the wisdom you need when arranging, for example, the stoichiometry and the duration time of a determinate reaction.

What do you consider your biggest achievement in your scientific career?
The biggest achievement is for sure the obtainment of molecules endowed with antibacterial activity since I believe drugs are important tools for the mankind's health.

How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
At the moment I am the only PhD under the supervision of my mentor, Assist. Prof. Nace Zidar.

What are the features of a successful PhD student or postdoc?
Persistence, creativity and a little dose of risk are the features I believe count most in the career of a PhD student.
Curiosity is also fundamental: I learnt how to predict and plot the physicochemical properties of my inhibitors while attending a summer conference.

How would you describe yourself as a supervisor?
I am not a supervisor, but I had some students working with me. I would describe myself as a methodical person because I consider the lab environment as a second house.

What is the most embarrassing thing you did in the lab while doing experiments?
The most distressing happening was when I mistook the labels of two similar compounds and it took several time to understand which one was the correct one. Another embarassing thing during the master thesis was while evaporating phosphorus oxychloride. The rotavapor contained few drops of water from a previous job and I suddenly noticed an evolution of smoke. I asked my mentor for help and except for the scare of seeing a "cloudy sky" I could go on with my experiments unharmly.
And yes, do not leave a black product on the bench without naming it: I found my product in the trash bin because a co-worker thought it was an impure mixture.

Which scientist do you admire the most and why?
My favourite scientist is Prof. Mitsunobu. His famous reaction that combines an alcohol and a carboxylic acid to make an ester has become one of the most important transformations in organic chemistry at industrial level and in academia. I have often carried out the Mitsunobu process and I believe one of its major utility is the inversion of configuration of the alcohol starting material.

Did you experience any unfair situations during your scientific career?
I did not experience such unfair situations. I think luck sometimes plays an important role in organic chemistry.

Which paper of yours you are the proudest of and why?
Without doubt the review whose title is "Overcoming problems of poor drug penetration into bacteria: challenges and strategies for medicinal chemists". It was my first publication and for me it represented a big achievement since I consider myself more a "laboratory guy" than a write-aholic.

Which field of medicinal chemistry do you consider the most promising in the future?
The discovery of novel anticancer and antibacterial agents. Finding novel anticancer drugs with limited side effects and antibacterial agents effective against resistant bacteria would represent a big step forward in the world of medicinal chemistry.

This week's #Iamamedicinalchemist is Fabrizio Giordanetto, Head Medicinal Chemistry from D E Shaw Research LLC.

What makes medicinal chemistry unique and so interesting? Read from below!

How did you get interested in Medicinal Chemistry?
I became completely hooked on Medicinal Chemistry when I heard a talk on Drug Discovery and Medicinal Chemistry given by a SmithKline Beecham Director at a career fair organized by the local university. I simply could not resist the unique mix of design, engineering rigor, uncertainty management and scientific method directly responsible for the creation of new medicines. The idea of being able to decide and manipulate matter at an atomic level of detail and see direct consequences in the lives of human beings felt so challenging, meaningful and rewarding, there was basically no coming back. Early thoughts about a career in architecture were quickly dispelled by the promise of designing and building something that nobody did before, nobody could see in action, but whose results could change life. I clearly remember this aura of wizardry and unknown beckoning me then, I just had to try and do it for a living.

What did you do then?
I signed up for a Masters degree in Medicinal Chemistry, then got myself a scholarship for a PhD in the same subject because I was thirsty for more. The industrial placement during my PhD was so life-inspiring and life-transforming it is hard to describe with words. I would leave the company site late at night desperately wanting back the next morning. The next day I would arrive fully energized despite set-backs, my sheer ignorance and the challenges ahead, daring to try again. A magic magnetic pull drawn me to data, new concepts, revised ideas, different people and skills, the details of all these aspects. It was never the same. There was so much to take in, to try and understand, to attempt practicing, to apply in projects, to internalize as an experience for the future, I only wished there were more hours in a day. It dawned on me I did not want to do anything else than taking one industrial drug discovery project after the other, sift through that complexity over and over again, success and constant learning as convincing beacons. I decided to build my professional path and all my future career decisions around it.

How is it now?
20 years on, I am so glad and grateful I made that choice and stuck with it. The reality of it surpassed everything I had imagined or even wished for. There is something extremely defining and inspiring in building a drug discovery project from scratch, when only the therapeutic modality is thought of, generating knowledge and expectations while advancing it through the various stages and pitfalls, all the way to progressive testing in humans. The journey itself is already worth all the efforts, let alone the final product. The fact that each project is truly unique and hardly resembles anything seen before only adds to the fascination. There is something very humbling in knowing and accepting that, despite all these years and all these projects, one would still have to start almost empty-handed, informed by past experience but not blinded by it, balancing endurance and pragmatism with finite resources and budgets, threading risk and opportunity, with final success still defined as a statistical exception.

What else could one wish for from a profession?

This weeks' #Iamamedicinalchemist is Ana Amic from the University of Josip Juraj Strossmayer in Osijek, Croatia. What does she enjoy about her job and other details you can read below.

How did you get interested in Medicinal Chemistry?
I was always interested in natural sciences, especially chemistry and biochemistry. Partly it was due to my teachers, but in a greater part it was due to my family. My father is a chemist, and he was the one who got me truly interested in chemistry.

Where and when did you obtain your master/PhD diploma?
I obtained by PhD diploma in the field of Chemistry in 2017 from the University of Josip Juraj Strossmayer in Osijek, Croatia.

What was/is the topic of your PhD project?
I was working on a novel and ecologically friendly method for N-acetylation of amines in choline chloride based deep eutectic solvents (DESs). The main objective was to create efficient and environmentally friendly protocol for acetylation using DES, which acts as a reaction medium as well as a catalyst. Developed protocol was proven to offer several advantages to conventional acetylation reactions such as operational simplicity, easy workup, shorter reaction time, excellent yield, economically and environmentally acceptable reaction conditions with the use of easily available, efficiently recyclable and reusable, nontoxic and bio-degradable solvents.

Where did you have your postdoc position? Or do you plan to pursue postdoc position?
I plan to pursue postdoc position, preferably in a combination of experimental and computational chemistry. Molecular modelling is a very useful tool that allows a better understanding of chemical and biochemical topics. It makes sense to use computers to predict characteristics of novel compounds and even the optimal route of their synthesis.

Where do you work at the moment and what is your current position?
Currently, I work at the Department of Chemistry at the Josip Juraj Strossmayer University of Osijek, as a Teaching Assistant.

What are your current research interests?
At the moment, I’m focused on computational chemistry and the use of computers to study reaction mechanisms behind biological activities of natural compounds, which can be found for example in medicinal plants. My research interests are in understanding of the background of biological activity of medicinally important compounds, determination of main structural characteristic of compounds responsible for such activity, and its application in development of novel and more efficient medicinally significant compounds. For example, one of my projects involves study of mechanisms of antioxidative activity of polyphenols and their metabolites; another one is a study of free radical scavenging mechanisms of 3-(4-hydroxy-3-methoxyphenyl)propanoic acid.

What do you like most about your job?
My job is dynamic, challenging and pushes me to do my best. It is a combination of teaching, continuous learning, creative and critical thinking and writing.

What kind of tasks your job includes?
There are two types of tasks in my current job. One is teaching practical courses and seminars for the undergraduate students, lab supervision, writing and grading exams, supervision of bachelor/master students, and similar. And the other is conducting my own research work and writing papers, conference presentations, etc. I’m trying to interest students for my research as much as possible, especially since this field of chemistry is not something they are well acquainted with and they are the next generation of scientists.

What kind of skills your job requires?
Teaching skills, wide knowledge, interpersonal and communication skills, organisational skills, team work, writing scientific papers, critical and logical thinking, ability to learn, problem solving, creativity, perseverance, …

What do you consider your biggest achievement in your scientific career?
I think that the biggest achievement in my scientific career is jet to come. It takes time and effort, so I’m constantly reading, learning and trying to improve myself.

How would you describe yourself as a supervisor/mentor?
So far I have supervised only a few undergraduate students and they are the only ones who can answer this question. But I understand the importance of a friendly working environment so I have always tried to be open for communication, patient, approachable, helpful and understanding.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
Well I’m quite boring so no explosions (yet), but I made a lot of silly mistakes, though nothing out of the ordinary. Except I have once accidentally wiped clean my memory stick (with no backup).

Which scientist do you admire the most and why?
Throughout the history there was a lot of excellent scientists worthy of admiration for their advanced thinking as well as for their perseverance, so it is difficult to pick just one (though I am a huge fan of Galileo Galilei). I admire the people in my research team because they are true experts in their field and are not afraid to share their knowledge and expertise. They are inspiring because of their passion, open-mindedness, integrity and honesty.

Did you experience any unfair situations during your scientific carrier?
This is something that occurs from time to time. I have had my share too, but I tend not to dwell on the past but use the experiences (even the negative ones) for the future.

Which paper of yours you are the proudest of and why?
The papers I am proud of are the ones that are a result of collaborations with friends. I was very proud of my first paper, but the most important paper is yet to come.

This week's #Iamamedicinalchemist is Cornelia Zumbrunn from Idorsia Pharmaceuticals in Allschwil (Switzerland). She is interested in developing drugs to fight deadly bacteria. Find out more of her research interests below!

How did you get interested in Medicinal Chemistry?
I have been fascinated by chemistry since the age of 14. After highschool and before university I worked for several months in a company producing UV stabilisors for car paint. I decided that the job itself was great but that I wanted to solve more relevant problems in life, i.e. save lives by discovering novel medicines.

Where do you work at the moment and what is your current position?
I work as a labhead and project leader at Idorsia Pharmaceuticals in Allschwil (Switzerland), a young but already quite big biotech company.

What are your current research interests?
Since the beginning of my career I have been convinced that antibiotics are one of the biggest achievements in modern medicine. I wanted to contribute to the discovery of novel drugs against deadly bacteria. This is what I have been doing since many years. Antibiotics cure infections and save lives. It is hard to imagine how our life would look like without them. Many of our recent innovations in healthcare such as surgery, cancer treatment, neonatal care etc. are based on the availability of antibiotics. At the same time, we, i.e. mankind, use antibiotics in an irresponsible way that favors the spread of resistance and we might soon experience again how it is to be unable to cure a pneumonia or skin infection.

I am grateful that despite the lack of return of investment a few pharmaceutical companies still feel the responsibility to invest money in this type of research.
More recently I have been involved in projects from other disease areas which of course does not change the overall aspects of my job.

What do you like most in your job?
I love the combination of practical work in the lab with the intellectual challenge to work in an interdisciplinary environment required to successfully develop a novel drug. To make compounds active on the target is one thing. But to synthesize compounds that are active, selective, non-toxic, stable, soluble and can be administered to patients in a reasonable way is a complete different thing. The job of a medicinal chemist is to understand these parameters and design compounds that fulfill all of those requirements. A formidable intellectual challenge, like a multidimensional Sudoku puzzle, which requires a lot of creativity! And a big frustration tolerance!

What kind of tasks does your job include?
I supervise a couple of technicians as well as an apprentice in my lab. In addition, I spend quite some time in meetings dealing with the advancement and coordination of the project

What kind of skills does your job require?
A medicinal chemist should not only master organic chemistry, but he/she should also be able to understand the biology relevant for the project. Knowledge of physiology, mechanisms of toxicity and metabolism as well as process chemistry, solid state chemistry and galenics are of great help. Working in big interdisciplinary teams requires a number of soft skills like communication and the awareness that the result is the achievement of the whole team and not of a single person.

What do you consider your biggest achievement in your scientific career?
I have been able to contribute to the advancement of several compounds into preclinical phase. This required sometimes a great deal of creativity and out of the box thinking, which I’m proud of. Unfortunately, none of these compounds has made it to the market. But I think that our job is to optimize the compounds as good as possible with as few compromises as possible. This is all we can do. Bad surprises in form of unexpected toxicity or intolerance are impossible to foresee and can arrive at any time.

Which paper of yours you are the proudest of and why?
The science I am most proud of has unfortunately never been published. This is one downside of my job: the most interesting compounds are patented and by the time we would be able to publish, the next project is important and writing a publication about the old one is time consuming and only “nice-to-have”.

This week's #Iamamedicinalchemist is Mohamed Mahgoub from South Valley University, Egypt. Read why he danced in the lab and other information about his work below!

How did you get interested in Medicinal Chemistry?
I got interested in chemistry when I was in secondary school. In the first year at university I became very excited in chemistry, especially organic chemistry. I always got high grads in organic courses and had good experience in laboratory. After graduation I received my permanent job at my science faculty as a Teaching Assistant…. Starting from this moment, I always was thinking how can I use my career to help people?! We have health problems not only in my country, but also worldwide. So, starting from that point I became interested in medicinal chemistry maybe I can do something for helping the humanity.

Where do you work at the moment and what is your current position?
I just came back from Lisbon university, Portugal. I was in a PhD scholarship. Now I am a Teaching Assistant at South Valley University (SVU), Egypt.

What are your current research interests?
Currently, find a novel acetylcholinesterase (AChE) inhibitors based on thiazolopyrimidines scaffold.

What do you like most in your job?
Working in the lab.

What kind of tasks your job includes?
There are many tasks, but the important things are:
1- teaching practical courses for undergraduate students and organized exams……etc.
2- doing my PhD work, searching, practical work and writing papers…….etc.

What kind of skills your job requires?
- Writing and reading scientific paper.
- Teaching skills.
- Seriousness, and of course if you are working in this filed you must be patient.

What do you consider your biggest achievement in your scientific career?
GREAT LEARNING___I think the biggest achievement was getting some scholarships, one after my master and two through my PhD studies. I learned many new things in my career (excellent characterization of new compounds using 1D and 2D NMR, ESI-MS and X-ray analysis, Molecular docking, some other computational chemistry (Optimization-Total energy- HOMO-LUMO orbitals, Hirschfeld surface …….. ect.).

What are the features of a successful PhD student or postdoc?
In my opinion is to love own work and working in a collaborative research group.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
So far, no explosion..!!! But there are some funny things happened during working in the lab. During the master I was trying to use new natural catalyst in my work. I tried several catalysts but did not work..!! Finally, I used Quartz as a catalyst and after 2h I found precipitate in the flask during heating….I was very happy and started dancing. My supervisor saw me and he started laughing ……It was funny day. Noteworthy, I finished my master by using this catalyst.

Which scientist do you admire the most and why?
Prof. Ahmed Zewail (http://www.zewail.caltech.edu/index.html) he is Egyptian. In 1999, He won the Nobel Prize in Chemistry alone! for his work on femtochemistry.

Which paper of yours you are the proudest of and why?
NOW, I am writing two papers and will be very proud after publishing.

Which field of medicinal chemistry do you consider the most promising in the future?
Drug design related to cancer disease in general.

For more information http://mahgoubchem.wix.com/mahgoub-chem

This week we present the story of Clemens Zwergel, a postdoctoral scientist at the Sapienza University of Rome.

How did you get interested in Medicinal Chemistry?
Standing as a child in the pharmacy of my aunt I was fascinated by the miracles happening in the pharmacy watching her dispensing all the coloured pills and creams. As I was growing my interests got more focused and I decided to become a healthcare professional studying pharmacy. At faculty of pharmacy, I met my first supervisor Prof C. Jacob getting me in touch with the world of science and research. He aroused my passion for medicinal chemistry while working on my diploma thesis with his unique character to motivate his students.

Where do you work at the moment and what is your current position?
I am a postdoctoral scientist at the Sapienza University of Rome in the Department of Drug Chemistry and Technologies. I am working in the team of Prof. Antonello Mai on various epigenetic targets.

What are your current research interests?
I am focused on the design and synthesis of small epigenetic modulators targeting all main classes readers, writers and erasers. For example, one of my current projects involves novel and selective HDACi in cancerous and non-cancerous diseases.

What do you like most in your job?
Certainly I like best the fact with my current job that I can combine practical work in the lab with creative thinking and writing. However I consider also teaching and advising students as a source of pleasure as these people are the next-generation scientists one can help to find their way.

What do you consider your biggest achievement in your scientific career?
That is not an easy question but I guess winning the Marie-Fellowship and thus doing my PhD project within an international network of experts was my biggest achievement so far.

What are the features of a successful PhD student or postdoc?
I would not limit this question only to PhD students and postdocs but to scientists in general. A good scientist needs to be a good all-rounder. He needs to possess not only creative skills and a strong working attitude but also practical skills are required to conduct the previously planned experiments. Problem solving strategies do not only help to get around scientific problems but also help with the interaction of colleagues and collaborators. Furthermore it is becoming more important also to be a marketing expert not only to promote the own career but also to attract sufficient funding.

What is the most embarrassing thing you did in the lab while doing experiments?
This story dates back well 12 years ago when I was still an undergraduate student. I was working in a team and I throwed away our product instead of the waste after 3 days of labwork. You can imagine that my team-mate was not very happy and also our instructor as we had to repeat all on an extra day. However I learned an important lesson: don’t throw away anything until you have your result.

Which scientist do you admire the most and why?
That is a tough question to name just one scientist because there are too many excellent ones, but you asked for one so my choice would be Leonardo Da Vinci. He influenced as universal talent our modern world we live in today in a way you cannot underestimate. His visons almost 500 years ago could be confirmed or became reality just now. He drafted not only the first idea of an helicopter but his contributions to anatomy were fundamental for our modern medicine of today.

What would you guess to be the next major breakthrough in medicinal chemistry?
In the years to come I expect the first multi-target modulators to be marketed. This intelligent approach usually allows scientists to avoid toxic side effects of single agents alone and reduce the risk of resistance development.

This week's #Iamamedicinalchemist is PhD student Teppo Leino from the University of Helsinki. Find out below why he is called Mr. Blue by his colleagues!

How did you get interested in Medicinal Chemistry?
I was interested in chemistry and other natural sciences already in high school, but only after starting the studies in the university I got really excited about organic chemistry. The professor at the university was teaching his topic with admirable enthusiasm, and he had an important role in getting me interested in medicinal chemistry. Also my first practical experiences in a medchem lab as an undergraduate were inspiring, and from then on I had the direction for the rest of my studies.

What are your current research interests?
I am interested in the studying the potential of azulene ring structure in medicinal chemistry.

What do you like most in your job?
Success in the lab! I experience the most exciting moments in my job, when I manage to synthesize a new compound and I get the first analysis results suggesting it to be what I wanted.

What kind of tasks your job includes?
Most of my job consists of research: both practical organic chemistry lab work and writing scientific articles. In addition, I have certain teaching duties such as supervision of M.Sc. students when they are doing their experimental work for their theses.

What kind of skills your job requires?
Creativity and strong understanding of organic chemistry and analysis of organic compounds. Not being a real skill, but I have learned patience is a must-have for a PhD student!

What do you consider your biggest achievement in your scientific career?
So far I think the biggest and most satisfying achievement in my career has been the publishing of my first article as first author. It was an important step on the way towards finishing the PhD and encouraged me to continue the journey.

What is the most embarrassing thing you did in the lab while doing experiments?
During my research visit in a foreign lab I was synthesizing new azulene derivatives, which are usually very colorful, thanks to the properties of azulene. Once an exothermic reaction got too hot and the pressure in the flask increased and caused the reaction mixture to explode in the fumehood. Following this, everything was colored blue in my hood and the colleagues started to call me Mr. Blue!

This week's #Iamamedicinalchemist is Federico Munafò who just finished his degree from the University of Pisa and who is looking for a Ph.D. position in the field. Read more about him and his research interests below.

What is your current position?
I am a just graduated in medicinal chemistry and pharmaceutical technology from University of Pisa and now I am looking for a PhD position. Meanwhile I am working in a laboratory where I perform chemical analysis on food contact materials.

How did you get interested in Medicinal Chemistry?
I have been addicted to chemistry since high school thanks to incredible teachers. During my last year I had the opportunity to spend some days in a research center where I met a research group focused on the development of polymers for medical uses. This meeting made me curious about application of chemistry in the medical field. That’s how I met medicinal chemistry and I fell in love with it. Figure out how a pill of a NSAID can ease the pain by applying organic chemistry is really amazing, isn’t it?

What are your current research interest?
My master thesis project, which has been carried out at the University of Copenhagen in the research group headed by Associate Professor Anders Bach, was focused on ischaemic stroke. Depletion of oxygen and glucose, due to blood flow reduction, initiates a series of biochemical reactions after minutes of ischaemia, together called ischaemic cascade, that lead to the production of reactive oxygen species, and at present the only available therapy focuses on restoring an adequate flow of blood to the brain without counteract oxidative stress. An emerging therapeutic strategy against ischaemic stroke is to disrupt the protein-protein interaction between Nrf2 and its repressor protein Keap1, thus boosting the Nrf2-dependent defence against oxidative stress.

What do you like most in your job?
Undoubtedly, I like to wake up in the morning without knowing what the day holds for me. I don’t want to write “see yesterday” every evening on my diary. This job gives the opportunity to do different things. One day you can be an organic chemist and the day after you can perform biochemical tests. Another aspect that I really like is that team work is the basis of this job. You cannot achieve results without the contribution of your workmates, but, at the same time, your work is fundamental to reach the goal. Finally, interdisciplinary meetings are always a good opportunity to learn something new.

What kind of task your job includes?
I work in a chemical synthesis laboratory. My tasks involves organic synthesis, characterisation and purification of compounds with different scaffolds, such as sulfonamides, benzo[7]annulene derivates, and benzotriazole derivates. Furthermore, I prepare presentations about my work for group meetings and I daily update my laboratory book.

What kind of skills your job requires?
From a professional standpoint, a good knowledge of organic chemistry and spectroscopy (mainly NMR and Mass Spectroscopy) makes the job easier. Except for these “standard” requires, I think that motivation, curiosity and perseverance are keys issue to succeed in this regard. Research is certainly fascinating, but quite often could be stressful. We should learn from failures. As is often said, bad results are still results. Well, you know, it is just the way life is. Another key require is the ability to work as a team. We must be cohesive team. As I said previously, you can not achieve results without the contribution of your workmates, but, at the same time, your work is fundamental to reach the goal.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
Sorry, I have not bombed any laboratory yet. However, once I was synthesising a new compound starting from a mercaptan and probably I did not close properly the reagent vial or the reaction vessel. What is certain is that a stench was smelled all around the laboratory. At the next group meeting we talked about the project...and why mercaptans have a disgusting smell.

Which scientist do you admire the most and why?
That’s a tough question. I admire for sure Giulio Natta. HIs studies leaded to the synthesis of polypropylene and we all well know the importance of this polymer in our daily life. I also admire Margherita Hack for her professional highlights, but mainly for her activities outside of science and her thoughts about ethic. Finally, I admire Alexander Fleming. I guess we all agree that his discovery changed the fate of a lot of people.

This week's #Iamamedicinalchemist is Nadine Jagerovic from Medicinal Chemistry Institute in Madrid. Read about her research below.

How did you get interested in Medicinal Chemistry?
After having defended my thesis which was oriented on materials, I was actually feeling that I could even enjoy more research if I could focus my chemistry on biochemistry, biology and medicine. It is why I did my postdoc in a medicinal chemistry lab.

Where and when did you obtain your PhD diploma?
I am originally from Beaune in France, and I obtained my PhD diploma in 1991 from the University of Burgundy. The research group was very dynamic and I really enjoy a kind of family atmosphere.

What was the topic of your PhD project?
I worked on metalloporphyrins. They are fascinating structures having precious colours. However, due to their instability to oxygen and water, once they were getting brown, you knew that the reaction needed to be set up again. The purpose was getting porphyrin-based polymeric conductors.

Where did you have your postdoc position?
I got my first two-years-postdoc position at the University of California Davis (USA) founded by a NIH grant. There, I could apply the porphyrin chemistry to the photodynamic therapy. This therapy was just emerging and it was so exciting to be part of the adventure. San Francisco was close, which only increased the pleasure to be postdoc.
Then I got my second two-years-postdoc position at the Medicinal Chemistry Institute in Madrid (Spain) thanks to a Marie-Curie-fellowship in the EU human capital mobility program.

Where do you work at the moment and what is your current position?
I reside in Spain and I have been working at the Medicinal Chemistry Institute in Madrid for more than twenty years. How time flies! I am a Senior Research Scientist of the Spanish Research Council.

What are your current research interests?
These last 15 years, I have been developing my research in the cannabinoid field. As a medicinal chemist, my research is focussed on designing new entities acting on the endocannabinoid system. Due to the increasing public interest for the medicinal cannabis, studying its mechanism of action and designing new molecules with reduced psychotropic effects is a personally fulfilled research.

What do you consider your biggest achievement in your scientific career?
The day that I think having accomplished my biggest achievement, I better stop doing research. There is no way to be satisfied, learning is the best achievement. Another kind of achievement for me is the pleasure realizing that my students are getting scientifically independent. This is probably my mother-hen side coming up.

How many PhD and postdoc students do you have at the moment?
Are you currently looking for a new PhD and postdoc students?
In the group, we have one PhD student, three graduates and soon another postdoc student. Depending on the grants or company contracts, we might offer PhD positions. But, be aware, the candidate is not only selected by myself, my students participate in this selection.

How would you describe yourself as a supervisor?
I never feel to be a supervisor. I am as my students are, part of the group. I usually prefer to let them develop their research and be there when they need me as an advisor. That does not stop me being mother-hen.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
I experienced fire, small explosion but the most embarrassing concerned a new computer. That was a long, very long time ago, I change my Mac computer for PC. The first day I clean the screen in my way and the next day I could not start the computer. A computer scientist took it to repair and two days later asked me who was the person that move the boot disks in a folder named “No idea”.

Which scientist do you admire the most and why?
I am a “fan” of Professor Mechoulam, the father of the THC (tetrahydrocannabinol). I admire him as researcher and as a person. This is one of the most generous person I know. He has been collaborating with hundreds of researchers. He is always smiling and full of energy despite his age. For years, he has been the research engine of all of us, he inspires most of us in the field of medicinal cannabis.

Did you experience any unfair situations during your scientific carrier?
We all experienced such situations from time to time, but this is always better not spending too much time and energy in it.
Which paper of yours you are the proudest of and why?
I am never fully proud of a paper, but I actually like the papers that are the results of several nice collaborations with friends.

Which field of medicinal chemistry do you consider the most promising in the future?
Personalized medicine is emerging. It will be so interesting to be able to treat patients based on their predicted response or risk of disease. Medicinal chemist can help in this direction with their expertise.

What would you guess to be the next major breakthrough in medicinal chemistry?
I hope that neglected tropical diseases and cancer can find treatments. In the case of the tropical diseases, Foundations as the one of Steve Job, finance international grants. For instance, research is currently in an advance stage with the existence of a cheap unique-dose antimalarial agent. Treatment of cancer will be personalized decreasing side-effects.

What is your current position?
I’m a last year PhD student in Medicinal Chemistry at Uppsala university

How did you get interested in Medicinal Chemistry?
I’ve always been interested in the natural sciences and in high school I had an outstanding chemistry teacher who really awakened my interest to the field of chemistry. He also gave me the opportunity to go to the Berzelius days, which is the biggest chemistry meeting for high school students in Sweden. One of the lecturers showed us the beauty of medicinal chemistry and from that day I was hooked! I really like the combination of organic chemistry with the medicinal field.

What are your current research interests?
My PhD project involves identification and synthesis of Insulin-regulated amino peptidase (IRAP) inhibitors. Inhibition of IRAP has been shown to improve cognitive functions in several animal models and is considered as a potential target for treatment of cognitive disorders. Previously, most of the inhibitors have been peptide-based but we developed an assay amenable for HTS where we identified several small molecule-based inhibitors. We’re currently working on hit expansions on some of these.

What do you like most in your job?
I really like that I get the opportunity to do so many different things. Synthetic organic chemistry, analysis and biochemical testing of the compounds, as well as teaching undergraduate students. I like spending time with motivated people in the lab even though we’re working in different projects and in different areas of the medicinal chemistry field. The interdisciplinary discussions are what I like the most since I learn new things all the time. It satisfies my curious side that wants to know and learn as much as possible! Working as a PhD student has also given me a lot personally. A major challenge with a PhD project is to work independently and to find new ideas to tackle problems, and that has made me grow both as a scientist and as a person. I have learned to deal with pitfalls as experiments don’t always go as planned, and to manage a research project both independently and in a team.

What kind of tasks your job includes?
My job includes 80% research and 20% teaching. The teaching commonly involves supervision of lab courses and seminars in organic chemistry for undergraduate students. The research part is my PhD project which involves both synthesizing compounds as well as evaluating them as inhibitors in biochemical assays. I am also responsible for the NMR-instrument at the department which involves nitrogen and helium filling as well a basic maintenance of the instrument and software.

What kind of skills your job requires?
Except for all the ”standard” skills required for someone working in academia, like scientific writing, critical thinking, creativity, teaching, ability to learn and comprehend new information etc., I would say that some of the most important things when working as a PhD student is to be able to praise the failure and be persevering and courageous! Failure is a normal part of the process and sometimes it feels like getting a PhD is more of a test of endurance rather than knowledge, and you need to be brave from time to time to do something with what others don’t agree if you feel the potential. Of course, you also need to be able to work independently, to keep track of things you do (you will do a lot!), to be patient and believe in yourself (things will go wrong even though you gave your best), and last but not least; learn to get things done.

What is the most embarrassing thing you did in the lab while doing experiments, e.g. explosions?
Oh, this will make me sound like the most boring chemist ever, but so far I have manage to carry out my research project without any major fireworks in the fume hood. So far so good...

Which scientist do you admire the most and why?
Can I pick three? I would say Marie Curie for being the first woman to win the Nobel prize (twice!), Galileo Galilei for putting science before religion which must have been hard at that time, and Charles Darwin for knowing that the evidence he had for natural selection would cause people to get upset but he stuck with his conclusions and time has proven him right.
In everyday life, I would say that I admire scientists that are truly experts in their field and without any concerns shares their vast knowledge, allows you to ask an infinite number of questions without feeling stupid, and inspires you to continue and keep a positive mindset no matter how many hurdles you face along the way.