IN MEMORIAM: PROF. FRANÇOIS DIEDERICH (ETH ZURICH, SWITZERLAND)
It was with great sadness that we learnt of the death of Professor François Diederich, Professor Organic Chemistry at ETH Zurich, Switzerland. EFMC regrets the loss of this outstanding scientist and presents its condolences to his family at this sad time.
After receiving his doctoral degree from the University of Heidelberg, Professor Diederich moved to the University of California at Los Angeles (UCLA) from 1979 to 1981 for postdoctoral studies. He subsequently became a research associate at the Max-Planck-Institute for medical research in Heidelberg, and in 1985, Professor Diederich joined the faculty of the Department of Chemistry and Biochemistry at UCLA as an associate professor (1985-1989) and as a full professor (1989-1992). In 1992 he was appointed Professor of Organic Chemistry at ETH Zurich. Recipient of many prestigious awards, Professor Diederich continued actively involved in research after his retirement in 2017.
In 2016, EFMC awarded Professor Diederich the Nauta Pharmacochemistry Award for Medicinal Chemistry in recognition for his outstanding contributions to the science of medicinal chemistry, including the understanding of non-bonding interactions involved in molecular recognition and their application in modern drug design. His scientific work is documented in more than 700 publications and beautifully describes interactions such as sulfur-aromatics, cation-Pi, fluorine interactions and halogen bonding that are actively used by many scientists around the world in the discovery of novel drugs. More recently, Professor Diederich joined EFMC’s Advisory Board, where he decisively contributed to the visibility of the medicinal chemistry and chemical biology community.
BEST PRACTICES IN MEDICINAL CHEMISTRY: PHENOTYPIC DRUG DISCOVERY IS AVAILABLE!
Phenotypic drug discovery (PDD) has contributed to the discovery of many innovative drugs and has received a growing attention over the last few years.
In this second Webinar by the EFMC Best Practices in Medicinal Chemistry Working Group, we present the opportunities and challenges of phenotypic drug discovery and share best practices used in industry and academia.
We hope this will help students, early career professionals as well as experienced researchers recognize the full potential of this fascinating approach and understand the key questions and challenges that need to be addressed to discover novel drugs from phenotypic approaches.
The webinar is accompanied with two case studies from the recent literature highlighting the application of some key aspects of PDD.
Slides can be downloaded here, and recordings are also available on the EFMC YouTube Channel.
The “literature spotlight” section of the newsletter will bring you a summary of the recently published research in a concise and readable way. Papers covering a range of medicinal chemistry and chemical biology from a variety of journals will be explored by Dr Clemens Zwergel (University of Rome, IT) from the Communication Team.
This seventh contribution will focus on the recently published review on Recent advances in epigenetic proteolysis targeting chimeras (Epi-PROTACs) by Tomaselli et al. in European Journal of Medicinal Chemistry.
Only in the last few years a new way to hit drug targets has been established. The so-called PROteolysis TArgeting Chimeras (PROTACs) approach involves heterobifunctional molecules capable of triggering the poly-ubiquitination of the protein of interest (POI) resulting in its degradation through the recruitment of the ubiquitin-proteasome system. In this way, via lowering the POI's intracellular levels, their functions are indirectly downregulated. This innovative approach can be virtually applied to numerous drugs at preclinical and clinical stages. Recently, PROTACs gained more and more interest in the field of epigenetics, where the so-called epi-PROTACS could serve as promising biochemical tools as well as provide innovative avenues for drug discovery.
In the present review, the authors presented a focused overview of the application of the PROTACs technology to the three main classes of epigenetic POIs: "writers", "erasers" and "readers" with a strong emphasis on medicinal chemistry aspects. They discuss in detail the design, preparation, and optimization of epi-PROTACs and their potential application, mainly in cancer, in comparison with classical small molecule epi-drugs.
Daniela Tomaselli, Nicola Mautone, Antonello Mai, Dante Rotili
Recent advances in epigenetic proteolysis targeting chimeras (Epi-PROTACs) Eur J Med Chem. 2020 Aug 18;207:112750. doi: 10.1016/j.ejmech.2020.112750.
CALL FOR NOMINATIONS - EFMC PRIZES 2021
To acknowledge and recognise outstanding young medicinal chemists (≤ 12 years after PhD) working in European industry and academia, EFMC established the "EFMC Prize for a Young Medicinal Chemist in Industry" and the "EFMC Prize for a Young Medicinal Chemist in Academia".
The two Prizes are given annually and consists of a diploma, € 1.000 and an invitation for a short presentation at an EFMC symposium.
The prize-winners will be invited to give oral communications at the XXVI EFMC International Symposium on Medicinal Chemistry and EFMC Young Medicinal Chemist Symposium (EFMC-ISMC 2021).
Applications and regulations can be found on https://www.efmc.info/prizes
Deadline for submission: January 31, 2021
CALL FOR NOMINATIONS - EFMC-YSN PHD PRIZE 2021
Because recognising excellence and merits is important since the early stage, the EFMC and the Young Scientists Network are proud to announce the second edition of the "EFMC-YSN PhD Prize".
The Prize will consist of a diploma, a free registration and a 500€ travel grant to attend an EFMC Symposium.
The prize-winner will attend the XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC 2021) and EFMC Young Medicinal Chemist Symposium (EFMC-YMCS 2021).
Applications and regulations can be found on https://www.efmc.info/ysn-phd-prize
Deadline for submission: January 31, 2021
GET TO KNOW MALIN LEMURELL, ASTRAZENECA, SWEDEN
In this edition, our #Iamamedicinalchemist is the winner of the 2020 UCB-Ehrlich Award for Excellence in Medicinal Chemistry, Dr Malin Lemurell from AstraZeneca, Sweden.
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 like to ask from other medicinal chemists?
We are innovative and solve very complex multiparameter challenges, but I’d like us to also focus more on improved ways in how we operate to help our business to be more environmentally sustainable.
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.
REPORT OF THE 1ST ITALIAN YOUNG MEDICINAL CHEMISTRY VIRTUAL MEETING – I-YMC-VMEET
The 1st I-YMC-VMEET Italian Young Medicinal Chemistry Virtual Meeting, held online in a total digital edition from 22nd to 24th July 2020, was an event sponsored by the European Federation for Medicinal Chemistry (EFMC) and organized by the Medicinal Chemistry division of the Italian Chemical Society (DCF-SCI). It was a novel concept of an online event designed to showcase the work and the discoveries of the very best young researchers in the fields of medicinal chemistry and chemical biology of the country in these hard times of social distancing due to COVID-19.
It attracted an audience of over 360 registered attendees who heard four keynote lectures, representing the Italian medicinal chemistry school postponed this year and industry, 10 oral communications by selected young researchers and an interesting roundtable. An online poster session hosted on Twitter gave the opportunity to 66 students to present their work in an innovative and unusual way, despite this new formula the quality of the science presented was extremely high. The online meeting also included 8 poster prizes and the selected winners presented their work with a 5 minutes Flash presentation, a new fast format similar to a ‘pitch’ and quite different from the classical flash presentation. Thanks to the YouTube channel of EFMC, the meeting reached a total of more than 3400 visualizations, from people of around 40 countries.
The keynote lectures have been presented by:
- Carmine Talarico (Dompé Farmaceutici, Italy)
The Exscalate4CoV project: how CADD is supporting the fight against SARS-CoV-2. A real journey from HPC to virtual reality
The winner for the best oral communication was Monica Viviano from the University of Salerno for presenting an excellent report about the Identification of novel pyrazole derivatives as inhibitors of lysine acetyltransferase p300.
The best posters that were selected by the scientific committee with the help of the Directors of the schools (ESMEC, SSPA, and NPCF) and the members of the roundtable were:
- Vittorio Canale (Jagiellonian University Medical College, Poland)
Efficient and sustainable synthesis of a potent and selective 5-HT7 receptor antagonist using a mechanochemical approach
- Laura Scalvini (University of Parma, Italy)
N-Acylethanolamine Acid Amidase (NAAA): Mechanism of Palmitoylethanolamide Hydrolysis Revealed by Mechanistic Simulations
- Chiara Lo Caputo (CERMN, France)
Design and synthesis of small molecules to disrupt XIAP/Caspase interaction
- Matteo Mori (University of Milan, Italy)
Investigating the inhibition mechanism and catalytic cycle of MbtI, the salicylate synthase from Mycobacterium tuberculosis
- Irene Brusa (University of Bologna Alma Mater Studiorum, Italy)
Hit optimization for the development of novel rnf5 inhibitors as a therapeutic strategy in cystic fibrosis
- Deborah Palazzotti (University of Perugia, Italy)
Small-molecule inhibitors targeting AKT1 active and allosteric sites
- Andreea Larisa Turcu (University of Barcelona, Spain)
A new therapeutic approach for Alzheimer’s disease: novel P2X7 receptor antagonists
- Greta Bagnolini (University of Bologna, Italy) – Social Prize Winner
Dihydroquinolone pyrazoline-based compound as a new RAD51-BRCA2 protein-protein disruptor to trigger synthetic lethality in pancreatic cancer
All received a sponsored mug and presented a flash communication.
The 1st I-YMC-VMEET concluded with a roundtable about Medicinal Chemistry Career. Moderated by Prof. Gabriele Costantino from University of Parma and with the interventions of: Yves Auberson (EFMC President) – Novartis, Switzerland, Kristina Goncharenko (EFMC-YSN) – SpiroChem, Switzerland, Rui Moreira (EFMC President Elect) – University of Lisbon, David Peralta (Editor-in-Chief, ChemMedChem) – Chemistry Europe, Germany. The round table began with the introduction of the speakers and then they showed the different careers in the medicinal chemistry field. Thanks to their experiences they were able to give full answers to the participants’ questions. Indeed, during the roundtable, participants had the opportunity to explore specific career issues including international opportunities in science, succeeding in pharmaceutical industry, tips on grant writing, considerations for scientists in Ph.D. careers, and exciting careers in the editorial field.
The real innovations of this meeting was, first of all, the special format designed for an online audience with brief lectures and half-day program, and second but not less important, the introduction of social activities online to strengthen the sense of community, promote socialization, and involve participants actively. The social activities were an aperitif via Zoom with all the participant and a special broadcasted event “BEYOND SCIENCE: Medicinal Chemistry Got Talent” where participant had the opportunity to show their talents beside medicinal chemistry.
The members of the organizing and scientific committees are grateful to all those companies who provided sponsorship for this ‘Totally Free’ meeting, without this help it would be impossible to realize this event. We gratefully acknowledge the valuable contributions of ChemMedChem, Biotage, Deltek, Exscalate4CoV, Evotec, Merck, Schrodinger, Zentek, S-IN Soluzioni Informatiche & Pharmacelera for their generous sponsorship of this online meeting.
We once again thank our invited speakers as well as all the enthusiastic participants who made this conference such a success. Poster session is still available via conference website (https://www.i-ymc-vmeet.it), and this is a permanent opportunity for discussion, networking, and establishing personal contact, after the meeting, that could contribute to consolidating the success of this event.
NEWS FROM THE BIOLOGICAL AND MEDICINAL CHEMISTRY SECTOR (BMCS) OF THE ROYAL SOCIETY OF CHEMISTRY (RSC)
The BMCS are pleased to announce the launch of our new website - https://www.rscbmcs.org. Please copy this into your favourites and use the link to access the latest information on BMCS activities, symposia and announcements
BMCS also remind all about the Malcolm Campbell Memorial Prize 2021 and announces various events.
REMINDER: Malcolm Campbell Memorial Prize 2021
Nominations should be submitted no later than 31st October 2020 to:
Maggi Churchouse, RSC-BMCS Secretariat, e-mail: firstname.lastname@example.org
For further details, please access the activities link on https://www.rscbmcs.org
Virtual MEETING - 31st Medicinal Chemistry in Eastern England (Hatfield symposium)
26th November 2020
NB Please note date change from previous MedChemWatch
Synopsis: Known colloquially as the "Hatfield MedChem" meeting, this is a highly successful, long-standing, one-day annual meeting. The meeting aims to be informal and interactive, and offers excellent scientific development and networking opportunities for all those working in medicinal chemistry and drug discovery
21st RSC / SCI Medicinal Chemistry Symposium
12th to 15th September 2021, Churchill College, Cambridge, UK
The call for abstracts will close on 20th November (short talks) and 30th April (posters – first round)
Synopsis: Europe’s premier biennial Medicinal Chemistry event, focusing on first disclosures and new strategies in medicinal chemistry
THIS NEWSLETTER IS KINDLY SPONSORED BY LIFE CHEMICALS
ISSUE SPONSORED BY
Life Chemicals is a fully integrated platform for early drug discovery that specializes in design and synthesis of novel screening compounds, focused libraries, fragments and building blocks. Our proprietary stock collection comprises over 500,000 original drug-like molecules. Custom synthesis, molecular modeling, scaffold-based library design and scale-up services are available.
EFMC ORGANISED EVENTS
August 29-September 2, 2021
EFMC-ISMC 2021 - XXVI EFMC International Symposium on Medicinal Chemistry
September 2-3, 2021
EFMC-YMCS 2021 - 8th EFMC Young Medicinal Chemists’ Symposium
Oegstgeest, The Netherlands
16th EFMC Short Course on Medicinal Chemistry - New Opportunities in GPCR Drug Discovery
EFMC CERTIFIED EVENTS
October 7-8, 2020
1st MercachemSyncom Digital Conference - Exploring New Modality Space by Precision Chemistry
EFMC SPONSORED EVENTS
November 5-7, 2020
18th Hellenic Symposium on Medicinal Chemistry (HSMC-18)
November 19, 2021
MedChem 2020 – Medicinal Chemistry in Belgium: Innovation and Success Stories
Principal Scientist I, Novartis Institutes for BioMedical Research, Analytics & Separations Basel, Switzerland
Tenure Track Assistant Professor at the Department of Biomedicine, Aarhus University, Department of Biomedicine Aarhus, Denmark
Associate Professor at the Department of Biomedicine, Aarhus University, Department of Biomedicine Aarhus, Denmark
Professor at the Department of Biomedicine, Aarhus University, Department of Biomedicine Aarhus, Denmark