MedChemWatch
Monthly Newsletter September 2021

THE CHEMICAL BIOLOGY-MEDICINAL CHEMISTRY CONTINUUM: EFMC’S VISION

We are happy to acknowledge the publication of the EFMC editorial on chemical biology, in ChemBioChem.

It discusses chemical biology as currently understood by EFMC, including all activities dealing with the design and synthesis of biologically active chemical tools, and their use to probe, characterize, or influence biological systems.

Research spanning chemical biology and medicinal chemistry is a rapidly evolving area, the dynamics of which are driven by new ideas, tools, and technologies emerging from a wide array of scientific disciplines.

Chemical biology has dramatically changed over the last few years and is now a mature field of science, and therefore a more precise definition of what it encompasses, especially for the EFMC, is necessary.

Read this freely accessible article and let us know what you think (link).

EFMC WELCOMES THREE NEW NATIONAL ADHERING ORGANISATIONS

In our aim to showcase the Chemical Biology/Medicinal Chemistry continuum, the EFMC is delighted to welcome three new additional national adhering organisations.

  • The Organization Pharmaceutical Research Institute of Bosnia & Herzegovina
  • The Chemical Biology group of the French Chemical Society (SCF)
  • The Society for Medicines Research, United Kingdom

We warmly welcome them into our federation, and we look forward to a fruitful collaboration in our common objective to advance the science of medicinal chemistry & chemical biology in Europe and around the World.

Have a look at the current list of national adhering organisations here.

LITERATURE SPOTLIGHT

The “literature spotlight” section of the newsletter will bring you a summary of the recently published research in a concise and readable way. Multiple thematics from different journals will be highlighted thanks to the valuable contribution of Kristina Goncharenko from the communication team.

This latest contribution will focus on the recently published article on “Identification of molecular glues of the SLP76/14- 3-3 protein–protein interaction”.

Protein–protein interactions (PPIs) are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. A novel and promising approach of the stabilisation of PPIs through molecular glues has been described by Soini et all.

In stark contrast to research in protein–protein inhibition, the field of stabilisation remains underdeveloped with comparatively few examples of small-molecule stabilisers of PPIs reported to date. At the same time identifying molecular glues has received much interest more recently, especially in the fields of targeted protein degradation and 14-3-3 PPIs. The hub-protein 14-3-3 has a broad interactome with more than 500 known protein partners that present a great opportunity for therapeutic intervention.

In this study Soini et all have developed an HTRF assay suitable for HTS of the 14-3-3/ SLP76 PPI and have completed a proof-of-concept screen against a chemically diverse library of 20K molecules. The adaptor protein SLP76 has been reported to interact with 14-3-3 proteins downstream of the TCR, playing an important role in mediating its own proteasomal degradation. Soini et all believed that stabilisation of this PPI could be exploited to potentiate degradation of SLP76 and therefore inhibit TCR signalling. This would represent an interesting alternative to other approaches in the field of targeted protein degradation. In this article 16 novel stabilisers of the 14-3-3/SLP76 PPI are disclosed across multiple different chemotypes. This approach could potentially be applicable to identify molecular glues with broad applicability in the field of 14-3-3 PPIs.

Lorenzo Soini, Martin Redhead, Marta Westwood, Seppe Leysen, Jeremy Davis and Christian Ottmann

https://pubs.rsc.org/en/content/articlelanding/2021/md/d1md00172h

EFMC PHOTO COMPETITION 2021 - BRIDGING MEDICINAL CHEMISTRY AND CHEMICAL BIOLOGY

To support the EFMC efforts to showcase the continuum between Medicinal Chemistry and Chemical Biology, we sought the help of our community with a request to share a picture representing their vision of "Bridging MedChem and ChemBio".

Thirty candidates met our challenge, submitting their picture to public voting at the occasion of the XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC).

Discover the winner and runners-up below!

Grabbing most of the votes, the winner is:

  • Souvik Sarkar (Umeå University, Sweden)

The two runners-up are:

  • Pallabi Sengupta (Bose Institute, India)
  • The PharmaChemistry Team of the Italian Institute of Technology (Italy)

Congratulations to them!

Browse all submitted pictures under this link.

GET TO KNOW STEPHANIE GUERET, ASTRAZENECA, SWEDEN

In this edition, our #Iamamedicinalchemist is the runner-up of the 2021 EFMC Prize for Young Medicinal Chemist or Chemical Biologist in Industry: Stephanie Gueret from AstraZeneca, Sweden.

Get to know her better by reading our interview below.

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 carry out your postdoctoral training?

After my stay in New Zealand, I returned to the Northern 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 a 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 products and the total synthesis of complex molecules which I found very fascinating.

What do you like best about your work?

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 concerns 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 and 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, disease-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 which is located on a narrow strip of land between the Pacific Ocean and the Tasman Sea. One day while I was quenching leftover potassium metal, I used a pissette of isopropanol which unfortunately had slowly sucked 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 the 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 for the quicker design of new molecules for a given target, to answer key questions and to advance drug discovery. It would allow analysis and extraction of trends from large datasets in order to learn and help evolve our design and understanding of the DMPK challenges.

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

#MedChemCASES - SEMINAR BY THE DIVISION OF MEDICINAL CHEMISTRY OF THE GERMAN CHEMICAL SOCIETY (GDCH)

The MedChem Division of the German Chemical Society (GDCh) would like to invite you to the next #MedChemCASES online seminar which will be held on September 23 by Dr Timo Heinrich (Merck KGaA, Darmstadt).

The topic of the webinar will be “Discovery and Optimization of Next Generation Reversible Methionine Aminopeptidase-2 Inhibitors – Identification of clinical compound M8891”

Co- and post-translational protein processing is important to ensure the maturation to functional proteins. MetAP-2 proteolytically removes the amino-terminal methionine from nascent proteins, and inhibition of its activity has been shown to block angiogenesis and tumor growth, suggesting that small-molecule inhibitors of MetAP-2 may be promising options for the treatment of cancer. This talk describes how persistence and serendipity helped to identify a previously unknown MetAP-2 inhibitory scaffold. The biochemical activity of more conventional, purine base compounds, did not translate to cellular activity. Thorough analysis of HTS screening results led to the identification of chiral tartronic diamide hits. Structure-based hit-to-lead optimization is outlined, including different synthetic strategies for most efficient access to improved derivatives as well as asymmetric approaches. The initial lead compound suffered from enterohepatic circulation, preventing further development. Binding kinetics were investigated by fluorescence cross-correlation spectroscopy and residence time on the target protein was one important characterization criterion. Adjustment of H-bond donor/acceptor count and multiparameter analysis of the compound properties led to the nomination of the clinical development compound M8891, which impedes the growth of primary endothelial cells, and exhibits dose-dependent biomarker modulation and antitumoral activity in mouse xenograft models.

Register for free here: https://zoom.us/webinar/register/WN_n1TxmudKQHC6Czfu0D8G4Q

#GDCh (MedChem Division), #NextGenMedChem.

NEWS FROM THE SOCIETY FOR MEDICINES RESEARCH (SMR)

SMR is announcing its upcoming online event: Covid-19 Preparing for Tomorrow | Lessons Learned from the International Frontline on September 9, 2021. This online international COVID-19 conference will bring together inspirational thought leaders from around the world to share their critical learnings on COVID-19.

An international panel of experts will distil the evidence and consider the key lessons learned during a series of stimulating presentations.

Discover the Programme!

  • Navigating a global response to the pandemic to develop a vaccine made for the world
    Professor Sir Mene Pangalos, Head of AstraZeneca R&D
  • The COVID-19 epidemic in the UK - the first 18 months
    Professor Graham Medley OBE, Professor of infectious diseases modelling, London School of Hygiene and Tropical Medicine
  • The story of the NHS in unprecedented times
    Professor Alan Salama, Professor of nephrology and honorary consultant nephrologist, University College London and Royal Free Hospital, London
  • JNJ journey to addressing urgent global need for a Covid-19 vaccine
    Professor Hanneke Schuitemaker, Janssen Vaccines & Prevention B.V, The Netherlands

Registration can be found under this link. Registration is free for this meeting.

NEWS FROM THE BIOLOGICAL AND MEDICINAL CHEMISTRY SECTOR (BMCS) OF THE ROYAL SOCIETY OF CHEMISTRY (RSC)

The BMCS announces some upcoming events:

  • 4th Artificial Intelligence in Chemistry (Poster deadline is August 13th)
  • 3rd RSC/SCI Symposium on Antimicrobial Drug Discovery
  • 5th RSC/DMDG/DMG New Perspectives in DMPK (Abstract deadline is November 25th)  

VIRTUAL - 4th Artificial Intelligence in Chemistry
27th and 28th September 2021
Website: https://www.rscbmcs.org/events/ai-in-chemistry/
Synopsis: Artificial Intelligence is presently experiencing a renaissance in the development of new methods and practical applications to ongoing challenges in Chemistry. The meeting will combine aspects of artificial intelligence and deep machine learning methods to applications in chemistry

VIRTUAL - 3rd RSC / SCI SYMPOSIUM ON ANTIMICROBIAL DRUG DISCOVERY
15th and 16th November 2021
Website: https://www.rscbmcs.org/events/antimicrobial/
Synopsis: Coinciding with WHO’s World Antibiotics Awareness week, this two-day meeting will examine the latest advances in antimicrobial drug discovery from a medicinal chemist’s perspective, focusing on the challenges associated with developing antimicrobials whilst also showcasing emerging strategies for tackling infection.

5th RSC / DMDG / DMG NEW PERSPECTIVES IN DMPK
22nd-23rd February 2022, Liverpool, UK
The call for abstracts will close on 25th November (oral) and 13th January 2022 (oral)
Website: https://www.rscbmcs.org/events/dmpk/
Synopsis: Members from across the DMPK research community are encouraged to join colleagues from across academic, industrial, and third-sector institutions and contribute to the ongoing discussion, evolution, and application of DMPK in various scenarios.

NEWS FROM EUCHEMS: RELEASE OF THE QUARTERLY “CHEMISTRY IN EUROPE” NEWSLETTER

The third issue of 2021 Chemistry in Europe (CiE) Newsletter is available online.

THIS NEWSLETTER IS KINDLY SPONSORED BY


 

ISSUE SPONSORED BY

WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries to advance discoveries and deliver groundbreaking treatments to patients. As an innovation-driven company, WuXi AppTec helps our partners improve the productivity of advancing healthcare products through cost-effective and efficient solutions. 

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EFMC CERTIFIED EVENT

October 12-13, 2021
Online
2nd Symeres Precision Chemistry Conference

EFMC ORGANISED EVENTS

September 9-10, 2021
Online
EFMC-YMCS 2021 - 8th EFMC Young Medicinal Chemists’ Symposium

May 8-11, 2022
Oegstgeest, The Netherlands
16th EFMC Short Course on Medicinal Chemistry New Opportunities in GPCR Drug Discovery

EFMC SPONSORED EVENTS

September 12-15, 2021
Online
21st RSC / SCI Medicinal Chemistry Symposium

October 5-8, 2021
Volgograd, Russia
5th Russian Conference on Medicinal Chemistry

October 20-22, 2021
Albacete, Spain
XIII Workshop of SEQT: Therapies with light and New Advanced Therapies

November 19, 2021
Liège, Belgium
MedChem 2021

EFMC SPONSORED SCHOOLS

September 13 – 17, 2021
Online
EUROPIN Summer School on Drug Design

September 22-24, 2021
Online
Summer School in Pharmaceutical Analysis (SSPA2021)

JOB PORTAL

Senior Scientist Core Facility for Mass Spectrometry, University of Vienna, Faculty of Life Sciences, Vienna, AUSTRIA
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Senior Scientist Core Facility for Cell Imaging & Ultrastructure Research, University of Vienna, Faculty of Life Sciences, Vienna, AUSTRIA
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Postdoctoral Researcher Toxicity Predicition & Data Science, University of Vienna, Department of Pharmaceutical Sciences - Pharmacoinformatics Research Group, Vienna, AUSTRIA
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Team Leaders - Medicinal Chemistry, BioAscent Discovery Ltd., Chemistry Newhouse, UNITED KINGDOM
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Scientists and Senior Scientists - Medicinal Chemistry, BioAscent Discovery Ltd., Chemistry Newhouse, UNITED KINGDOM
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Postdoc in chemical biology / biophysics, Louvain University, Louvain Drug Research Institute, Brussels, BELGIUM
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Post-doc and PhD Positions in Chemical Biology and Drug Discovery, EPFL, Institute of Chemical Sciences and Engineering, Lausanne, SWITZERLAND
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Drug Hunter @Aqemia, Paris, FRANCE
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