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.

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.

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.

https://www.sciencedirect.com/science/article/abs/pii/S0223523420307224

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

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

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.

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:

• Alfonsina D’Amato (University of Milan, Italy)
  OMICS profile of SARS-Cov2 
  Representing the European School of Medicinal Chemistry (ESMEC)

• Tiziano Bandiera (IIT Genova,  Italy)
  Market watch: novel drug approvals for 2019
  Representing the Summer School in Pharmaceutical Analysis (SSPA)

• Rita Petracca (Imperial College London, UK)
  RaPID Selection of Novel Macrocyclic Peptides as Modulators of Rab27a-effector Interactions
  Representing the 13th Young Medicinal Chemist’s Symposium NPCF

• 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.

REMINDER: Malcolm Campbell Memorial Prize 2021

Nominations should be submitted no later than 31^st October 2020 to:

Maggi Churchouse, RSC-BMCS Secretariat, e-mail:  maggi@maggichurchouseevents.co.uk

For further details, please access the activities link on https://www.rscbmcs.org

 #BMCS_MCMP

Virtual MEETING - 31^st Medicinal Chemistry in Eastern England (Hatfield symposium)

26^th November 2020

NB Please note date change from previous MedChemWatch

Website               https://www.maggichurchouseevents.co.uk/bmcs

Twitter                 #HatfieldMedChem20

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

21^st RSC / SCI Medicinal Chemistry Symposium

12^th to 15^th September 2021, Churchill College, Cambridge, UK

The call for abstracts will close on 20^th November (short talks) and 30^th April (posters – first round)

Website:  http://www.rsc.org/events/detail/42821/21st-rsc-sci-medicinal-chemistry-symposium

Synopsis:  Europe’s premier biennial Medicinal Chemistry event, focusing on first disclosures and new strategies in medicinal chemistry