Winning Picture: Chemical Symphony: A Vivid Glimpse into the Microcosmos. Credits: Exequiel Porta

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 one 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 one 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 would 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 two times Nobel prizer 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 Design-Make-Test-Analyse cycle (). I expect a real breakthrough of artificial intelligence in the years coming.   

With the aim to make this rich chemical resource accessible to a broader scientific community and to allow chemists to uncover novel bioactivities of their compounds, the publicly funded open-access initiative EU-OPENSCREEN offers chemists the opportunity to make their compounds available, in a regulated and transparent framework, to a wider community of biologists, who test these compounds in suitable bioassays. By doing so, chemists can expose their compounds to a broad range of different biological/drug targets to uncover the unknown bioactivities of their compounds, which would otherwise not be practical through individual one-to-one collaborations. Once a compound has been identified as a validated hit compound, a research collaboration between the chemist (who submitted the compound) and the biologist (who developed the bioassay) can be initiated.

EU-OPENSCREEN’s ca. 30 academic partner institutions offer complementary expertise and instrumentation to collaboratively develop novel chemical probes for the life sciences community. Primary screening data are made available to the scientific community through its open-access European Chemical Biology Database. EU-OPENSCREEN also promotes knowledge sharing within life science by organizing webinars and training activities, and by co-organizing the biennial European Chemical Biology Symposium.

Bruton’s Tyrosine Kinase (BTK), a cytoplasmic tyrosine kinase, is selectively expressed in a subset of immune cells, including macrophages, mast cells, and B cells. BTK is a key regulator of B cell antigen receptor signaling in B cells and of Fc receptor signaling in mast cells and macrophages.  It is likely that a BTK inhibitor will have a positive impact on autoimmune diseases which are caused by autoreactive B cells and immune-complex driven inflammation.

First generation BTK inhibitors have been approved for the treatment of B-cell malignancies, but their use is associated with adverse events due to inhibition of off-target kinases.

The presentation will cover the design, characterization, and medicinal chemistry optimization of a series of highly selective covalent BTK inhibitors stabilizing an inactive confirmation of BTK. The efforts resulted in the identification of remibrutinib (LOU064) as a highly potent inhibitor with a best-in-class selectivity profile. Remibrutinib showed high potency and was well tolerated in Ph1 and Ph2 clinical trials and is currently in Ph3 clinical studies for chronic spontaneous urticaria and multiple sclerosis. We will report the preclinical profile as well as clinical data of remibrutinib.

Register for free here.

#GDCh (MedChem Division), #NextGenMedChem.

Hot Topics: Targeting RNA
30^th November 2023, Virtual

Registration is now open!

Website: https://www.rscbmcs.org/events/hottopicsrna23/

Synopsis: The BMCS Hot Topics online meetings are intended to highlight breaking areas of research in fields of science relevant to drug discovery. They will run as stand-alone half-day virtual events, 2-3 times per year.  The programme will be targeted towards researchers working in academia or industry who would like to enhance their understanding of these nascent or developing fields.  The inaugural meeting will cover relevant methods and modes of targeting RNA in drug discovery and will focus on how small molecules can accomplish this, including RNA binding and degradation, splicing modulation, and enzymes modifying RNA. There will be presentations from leading academics and industry.

RSC-BMCS Postgraduate symposium XVII

7^th December 2023, University of Oxford, Oxford, UK

Abstract submissions are now open!

Registration is now open!

Website: https://www.rscbmcs.org/events/psxvii/  

Synopsis: This face-to-face meeting will comprise an oral and poster presentations from PhD students and post-doctoral workers researching in biological or medicinal chemistry. In addition, the agenda will feature invited keynote speakers from industry and academia.

9^th RSC-BMCS Fragment-based Drug Discovery Meeting
3^rd – 5^th March, 2024, Hinxton Hall Conference Centre, welcome Genome Campus, Cambridge, UK

Abstract submissions and registration is now open!

Website: https://www.rscbmcs.org/events/fragments24/

Synopsis: The aim of the 9th 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 this theme in having over three-quarters of the presentations focused on case studies. This will be complemented by technology progress in high concentration, NMR, SPR and X-ray screening.

BMCS Conformational Design in Drug Discovery

7^th March, 2024, GSK, Stevenage, UK

A date for your diary!

Website: https://www.rscbmcs.org/events/1dscd/

The BMCS Mastering MedChem VIII: 8th RSC-BMCS Symposium on Mastering Medicinal Chemistry

15^th March, 2024, Burlington House, London, UK

Registration is now open

Website: https://www.rscbmcs.org/events/mastermedchem24/

Synopsis: Mastering Medicinal Chemistry VIII is the latest in an ongoing series of conferences intended to provide expert advice and guidance to new practitioners in the field of drug discovery. It has been said that “there are two types of drug discovery programmes: those that hit serious problems and those that are going to hit serious problems”. Anticipating and preparing for such problems thus accelerates the delivery of new medicines: this event will feature presentations from experienced ‘drug-hunters’ in both industry and academia, who will talk about the challenges faced in modern drug discovery, and will share best practice common to all successful medicinal chemists.

35th Medicinal Chemistry in Eastern England (Hatfield symposium)

25^th April 2024, Fielder Centre, Hatfield, UK

Date for your diary!

Synopsis: Known colloquially as the “Hatfield MedChem” meeting, this is a highly successful, long-standing, one-day meeting that runs annually. The scientific program will comprise presentations showcasing medicinal chemistry case studies from tools to candidates, across a range of modalities, therapeutic areas and target classes, as well as covering more general topics at the forefront of drug discovery. The meeting aims to be informal and interactive, and is ideal for all those working in medicinal chemistry and drug discovery more widely.

3rd RSC / SCI / SEQT New Therapeutics for Global Health
19^th – 21^st June 2024, GSK TresCantos, Madrid
RSC/SCI/SEQT
Registration will be open soon! Keep checking website for updates!
Website: https://www.rscbmcs.org/events/ntgh24/
Synopsis: Tuberculosis, malaria and diseases caused by a diverse range of pathogens, including flaviviruses (eg dengue, West Nile), kinetoplastids (causative agents of Chagas disease, leishmaniasis, etc) and gut pathogens (worms, bacteria, parasites), remain a cause of high mortality across the globe. Fortunately, an ever-improving understanding of the complex life-cycles of these disease-causing pathogens is presenting increasing opportunities for those seeking to tackle these global health problems.

9^th GPCRs in Medicinal Chemistry
2^nd – 4^th October 2024, Evotec Campus Levi-Montalchini, Verona, Italy
RSC/SCI

Registration will be open soon! Keep checking website for updates!
Website: https://www.rscbmcs.org/events/gpcrs24/ 

Synopsis: The key role of G protein-coupled receptors (GPCRs) in human disease underpins their importance to modern medicine. We were pleased to hold this 9th meeting in the series on GPCR drug discovery, which combined cutting edge medicinal chemistry with innovative structural biology and novel drug design approaches.