MedChemWatch
Monthly Newsletter December 2018

Workshop at the European Parliament: EFMC as the voice of medicinal chemistry in Europe. (Editorial by Yves P. Auberson, EFMC President)

EFMC represents a research community that plays an important role in society. By providing tools to better understand the biology of human diseases and developing new drugs, chemical biologists and medicinal chemists can address issues that represent a huge burden to patients, families and social welfare. In particular, there is an enormous need for improved treatments of neurodegenerative diseases, such as Parkinson’s disease.

Our recent workshop in Brussels “Parkinson’s disease: understanding the causes to find a cure” was co-organized with EuChemS, alongside Members of the European Parliament, and representatives from the European Commission and the European Food Safety Agency (EFSA). The workshop aimed to increase awareness of both patients and researchers needs, as well as review the latest understanding of the causes of the disease. Further information on this event is available in the press release, and all presentations can be viewed at https://www.euchems.eu/parkinsons-disease-causes-and-cures-workshop/

By participating in such activities, EFMC both supports the cause of patients and helps increase awareness of the need for research funding, and for policies facilitating the task of our scientific community to address these complex issues. Please take advantage of this event to share our efforts within our network, and let people know that EFMC really cares.

With the New Year approaching, change is in the air for the EFMC website…

Our old and ever-faithful website (www.efmc.info) has been delivering news about events and activities of EFMC and of its National Adhering Organisations for a number of years. However, times are changing, and it is beginning to show its age. In a constantly evolving world, full of tablets and smartphones, we need a simpler, smarter and mobile responsive website to work on all platforms

The good news is that our team has been hard at work and is preparing for the launch of the website in January, so stay tuned…!

Exclusive Interview with Christa Müller, winner of the 2018 Nauta Pharmacochemistry Award for Medicinal Chemistry and Chemical Biology

Christa Müller from Bonn University is celebrating her 20th year as a Professor of Pharmaceutical Chemistry! We congratulate her for this big achievement and share her thoughts on medicinal chemistry.

How did you get interested in Medicinal Chemistry?

When I was an undergraduate student at Tübingen University, Prof. Hermann J. Roth presented an excellent lecture on Pharmaceutical Chemistry. Later, I chose him as my PhD supervisor and mentor. During that time I spent much time in the library of our institute, and there my favourite journal was the Journal of Medicinal Chemistry, which I loved to read. And I dreamed of publishing myself in that journal.

Where and when did you obtain your PhD diploma?

I completed my PhD in 1988 at the University of Tübingen, a small town in the State of Baden-Württemberg, in the South of Germany, about 60 km north of the city where I was born (Rottweil).

What was the topic of your PhD project?

Synthesis and properties of chiral amphiphiles and liposomal prodrugs with unsymmetrically substituted disulfide bridge. The compounds that I synthesized had terrible physicochemical properties. But I learned a lot about stereochemistry, prodrugs, lipids, amphiphilic compounds, liposomes and cancer therapy.

Where did you have your postdoc position?

At the National Institutes of Health in the Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, in Bethesda, Maryland, USA with Dr. John W. Daly. That was a whole new world for me which I had the privilege to discover. I would recommend everybody to work for some time in a top laboratory abroad, preferably on a different continent. You will have a new view on your previous work and life from a distance.

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

I have been a Full Professor of Pharmaceutical Chemistry at Bonn University since 1998 – for exactly 20 years. And I still enjoy the possibilities as a University Professor at one of the top German universities.

What are your current research interests?

My scientific interests are focused on the medicinal chemistry and molecular pharmacology of purine-binding membrane proteins (purine receptors, ectonucleotidases) and orphan G protein-coupled receptors. Disease indications include neurodegenerative and inflammatory diseases, cancer, and rare diseases. My activities are ranging from basic research to collaborative drug development projects with pharma industry partners. Recently I have become interested in new modalities in drug development.

What do you like most in your job?

Working with young, talented people and sharing my insights with them; contemplating about tricky scientific question and difficult issues - and finding solutions; contributing to the development of drugs that are beneficial for patients; collaborating with experts from different areas and from all over the world; reading scientific literature and learning something new every day.

What kind of tasks your job includes?

Teaching, research and administration

What kind of skills your job requires?

You have to be an allrounder and a hard worker; it requires creativity, organisational skills, problem-solving and leadership ability, team-working and collaboration competencies, teaching qualities, high motivation, patience, persistence, resilience - and you have to deeply enjoy what you are doing.

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

Actually, I have always been broadly interested and contributed to different areas related to medicinal chemistry.
• Together with my coworkers and collaborators, I have developed many tool compounds for a variety of receptors and enzymes, that are nowadays widely used in many labs all over the world. Since I have been working at Bonn University, we name them PSB (Pharmaceutical Sciences Bonn) compounds (e.g. PSB-603, a potent and selective adenosine A2B receptor antagonist).

• I created a proprietary compound collection at Bonn University – the PharmaCenter Bonn compound library - which even contains the compounds that I had synthesized for my PhD. We do not only collect compounds prepared in Bonn, but also those from other groups. If we identify a screening hit for a target of interest, we collaborate with the colleagues that provided the hit compound.

• Recently, we developed the first potent and selective antagonists for the orphan G protein-coupled receptor GPR17, which bear great promise for the disease-modifying treatment of demyelinating diseases such as multiple sclerosis (MS). Patents have been filed and the compounds are being developed in collaboration with a pharmaceutical company. If clinical trials are successful, this could change MS patients‘ lives.

• Early in my carreer I have developed synthetic methods, which are useful and are nowadays applied in a number of labs, e.g. the synthesis of 3-substituted 6 aminouracils, which are important precursors for xanthine derivatives (Müller, C.E., Tetrahedron Lett. 1991, 32, 6539).

• My group has developed a number of new assays for various targets. 

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

My group is quite big, but this is necessary for our approach which combines chemistry and biology. The techniques established in my lab range from synthetic chemistry, (bio)analytical studies, and molecular modeling to in vitro pharmacology, and molecular and structural biology.

I have 20 PhD students, currently more than usually, but several students are about to complete their thesis, and it is always good to have some overlap on a topic in order not to lose the knowledge regarding certain lab techniques.

If excellent students and postdocs apply to my lab, I always try to find a way to finance them.

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

High motivation is most important, in addition to creativity and talent, and persistence.
Regarding a young scientist‘s CV it is always good to have publications (quality is more important than quantity), to have shown mobility, and to be supported by previous supervisors.

How would you describe yourself as a supervisor?

Since I have a big group, I am not closely controlling each student. The students and postdocs will get some freedom to develop themselves as scientists, e.g. to realize some of their own ideas. In the inital phase, they will be co-supervised by a postdoc in the lab. I am always approachable to discuss results or problems and to suggest solutions, and I am carefully watching the progress of each project, and interfere if necessary to push it into the right direction and to make it successful. I do care for my students and coworkers.

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

I had (small) explosions and fires. Once, I upscaled a reaction from a 10 g to a 30 g scale, it was the regioselective alkylation of silylated uracil with propargyl bromide in the presence of iodide, the procedure that I had invented. After the reaction was completed, and the excess of the silylation reagent had been removed by evaporation, the silylated product was carefully hydrolyzed by the addition of ice-water. This is an exothermic reaction, and it became too hot, resulting in violent reaction involving the triple bond. Fortunately, the fire was under the hood and could quickly be controlled, with the help of my labmate.

Which scientist do you admire the most and why?

Marie Curie. She was the first woman to get a Noble Prize in science, and later on, she even got a second one. She achieved this as a Polish immigrant in Paris, at a time when women hardly had a chance to study.

Did you experience any unfair situations during your scientific career?

Yes, but I was also lucky. In fact, I was the first woman who got a full professorship in Pharmaceutical Chemistry in Germany, and I got this chance only because at that time, in the late 1980s, it was more attractive to take a job in industry than to stay in academia. 
Luckily, the University of Bonn had had good experiences with female science professors, and they offered me a chair without hesitation.
My perception is that not always the best scientists are successful, but the ones who are well connected within networks. The way you are treated is not always fair. On the other hand, data bases creating (more or less) objective assessments, nowadays can help in supporting fair decisions.
Another problem I have observed and encountered is envy, which can be very destructive. There seems to be increasing egoism and ruthlessness in parts of the younger generation.

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

Difficult to select because I have published around 400 papers so far, and there are a number of papers which I am proud of, including three publications which I co-authored and which were published in Nature.

Since I am supposed to select only a single paper, I would select this one:

Thomas Borrmann, Sonja Hinz, Daniela C. G. Bertarelli, Wenjin Li, Nicole C. Florin, Anja B. Scheiff, Christa E. Müller; 1-Alkyl-8-(piperazine-1-sulfonyl)phenylxanthines: development and characterization of adenosine A2B receptor antagonists and a new radioligand with subnanomolar affinity and subtype specifity. J. Med. Chem. 2009, 52, 3994-4006.

This manuscript describes adenosine receptor antagonists with low nanomolar affinity including the preparation of an A2B-specific radioligand. It contains a lot of information (which easily could have been divided into two or three papers, but I prefer papers with broad content). The described antagonists, e.g. PSB-603 and [3H]PSB-603, are currently among the most frequently used A2B antagonists due to their high potency, selectivity and metabolic stability. A long time after we had developed the first A2B-selective antagonists, such compounds have recently become of great interest for the (immuno)therapy of cancer.

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

• Immunotherapy of cancer using small molecules, in combination with targeted cancer therapies. 
• Personalized drug therapy and diagnostics.
• Artificial intelligence and computational approaches
• Structural biology – insights into drug-target interactions

What would you like to ask from other medicinal chemists?

• Which fields of medicinal chemistry would you consider the most promising in the future?
• How do you select the right targets?
• How did you manage to found a company (this is something I have not achieved yet) - and what are your recommendations?

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

Small molecules are clinically successful and will be approved for the immunotherapy of cancer - further revolutionizing cancer therapy.


Report of the 2nd Employment survey for European Chemists is out!

The report of the 2nd Employment Survey for European Chemists (ESEC2) has just been published. The report, which analysed data received in 2017, from a total of 2754 chemists and chemical engineers, delves into the employment conditions and career opportunities for chemists in Europe.

The figures take a look at a variety of aspects, including education levels, career planning, job satisfaction, employment sectors and salaries. The conditions and opportunities are individually analysed for all countries with a stastistically significant number of responses. The results in turn provide important clues for careers in these countries, and in Europe as a whole. This is the first general evaluation of the survey and provides many details about the chemistry workforce in Europe and its development. The ESEC2 is based on the experience of the first European employment survey (ESEC1) which was carried out in 2013, although both the questionnaire and the technology have been much reworked. The report was prepared by Reiner Salzer.

More from EFMC Photo Competition 2018

As we are preparing to launch the 2019 edition of the EFMC Photo Competition, celebrating the «International Year of the Periodic Table», we would like to highlight once more some of the amazing entries for the 2018 Photo Competition.

Can’t wait for more!? Discover them all on https://www.efmc.info/photocompetition

  One in one million – Luis Carvalho
As medicinal chemists we must go through thousands and thousands of compounds until we find a molecule with the perfect profile to become an approved drug. Every molecule we synthesize could revolutionize our field, but it sometimes feels like it's one in a million. That is what the Medicinal Chemist endures.
  Blue moon - Constantinos Neochoritis
Research on quinolinones for a specific medchem target yielded this nice picture; This derivative was isolated as white powder in which under ultraviolet light, it fluoresces blue.
  Sailing at the lab - Saylam Merve
All you need is a filter paper, plenty of methylene blue solution and a little sea sand to bring sea to your lab.


 

News from the Biological and Medicinal Chemistry Sector (BMCS) of the Royal Society of Chemistry (RSC)

The BMCS is happy to announce the following events

7TH RSC-BMCS FRAGMENT-BASED DRUG DISCOVERY
24th to 26th March 2019, Churchill College, Cambridge, UK

RECENT PROGRESS IN INTEGRIN-TARGETED DRUG DISCOVERY
28th March 2019, Royal Society of Chemistry at Burlington House, London, UK

PRESENT YOUR RESEARCH AS A POSTER AT THE 20TH RSC / SCI CAMBRIDGE MEDCHEM SYMPOSIUM
8th to 11th September 2019 at Churchill College, Cambridge, UK

7TH RSC-BMCS FRAGMENT-BASED DRUG DISCOVERY
24th to 26th March 2019, Churchill College, Cambridge, UK
The call for poster abstracts will close on 1st February 2019
Website: http://www.rsc.org/events/detail/33945/fragments-2019-7th-rsc-bmcs-fragment-based-drug-discovery-meeting
Synopsis: The aim of the 7th RSC-BMCS Fragment-based Drug Discovery meeting will be to continue the focus on case studies in Fragment-based Drug Discovery that have delivered compounds to late stage medicinal chemistry, preclinical or clinical programmes. The Fragment series was started in 2007 and continues with the theme, having over three-quarters of the presentations focused on case studies. The conference will include successful examples from all types of fragment-based approaches, including high concentration, NMR, SPR and X-ray screening

RECENT PROGRESS IN INTEGRIN-TARGETED DRUG DISCOVERY
28th March 2019, Royal Society of Chemistry at Burlington House, London, UK
The call for poster abstracts will close on 31st December
Website: http://www.rsc.org/events/detail/30991/integrin-targeted-drug-discovery
Synopsis: Integrin targeted therapeutics have been under investigation for some time, but few compounds have made it to / remained on the market due to side effects or lack of efficacy. Given the more recent structural insights, better understanding of downstream pathways, and potential application to a range of therapeutic areas, there has been a resurgence of interest in integrin inhibitors. This symposium will bring together researchers in this area to provide both a historical overview and recent progress in designing the next generation of integrin inhibitors

PRESENT YOUR RESEARCH AS A POSTER AT THE 20TH RSC / SCI CAMBRIDGE MEDCHEM SYMPOSIUM
8th to 11th September at Churchill College, Cambridge, UK
Deadline date for poster abstracts out soon
Website: http://www.rsc.org/events/detail/35363/20th-sci-rsc-medicinal-chemistry-symposium
Synopsis: The 20th symposium is one of the premier biennial Medicinal Chemistry events, focussing on first disclosures and new strategies in Medicinal Chemistry. This conference will be of interest to both academic and industrial scientists engaged in all aspects of the drug discovery and development process

News from the European Chemical Society (EuChemS)

Please find below the link for applicants for both EuChemS awards are currently open, namely:

Call for EuChemS Lecture Award

Call for EuChemS Award for Service

Deadline: 31 December 2018

You are also kindly invited to read the fourth issue of the 2018 Chemistry in Europe Newsletter. It is available online: https://www.euchems.eu/newsletters/chemistry-in-europe-2018-4/

The newsletter includes a number of interesting and highly relevant contributions, news, and upcoming events, such as an editorial by Robert Parker, RSC CEO and Member of the Executive Board on the recent EuChemS Chemistry Congress in Liverpool; an analysis on Open Education; input from the European Young Chemists’ Network and the Professional Networks; as well as news concerning the new Periodic Table we published, and a summary of the online course on Good Chemistry. Please also note that the nominations for the EuChemS Lecture Award and the EuChemS Award for Service are now open until December 31st.  

This month’s highlighted MedChemComm article - Probing the hras-1Y i-motif with small molecules

The article we’ve chosen for the MedChemComm article of the month is linked below. John Schneekloth Jr et al. report the first example of small organic compounds that directly interact with the hras-1Y i-motif, an important regulatory element of the HRAS oncogene promoter.  It is one of the first articles published in the ongoing ‘Molecular Pharmacology’ themed collection, highlighting the latest advances in the understanding of drug action at the molecular level and the exploration and application of emerging pharmacological modalities.

Read the article!

The latest edition of MedChemComm, the official journal of the EFMC, is available at:

MedChemComm

 

EFMC SPONSORED EVENTS

February 20-22, 2019
Paris, France
26th Young Research Fellows Meeting

March 6-8, 2019
Frankfurt, Germany
EUFEPS Annual Meeting 2019

March 13, 2019
Windlesham, United Kingdom
5th RSC-BMCS Symposium on Mastering Medicinal Chemistry

March 28, 2019
London, United Kingdom
Integrin Targeted Drug Discovery

June 27-30, 2019
Prague, Czech Republic
11th Joint Meeting on Medicinal Chemistry

EFMC ORGANISED EVENTS

April 28 - May 1, 2019 
Oegstgeest (near Leiden), The Netherlands
15th EFMC Short Course on Medicinal Chemistry - Strategies in Fragment Based Drug Discovery

June 10-13, 2019 
Krakow, Poland
EFMC-ACSMEDI MedChem Frontiers 2019

Find us on social media

EFMC Facebook EFMC Twitter EFMC LinkedIn EFMC Instagram

EFMC