How did you get interested in Medicinal Chemistry?

I am trained as a pharmacist and obtained my Masters in pharmaceutical sciences in 1988. During my six months internship, I realized that, although working in a community pharmacy is an important job with a big social impact, I wanted to do something else with my life. I was attracted to research, and mostly to the chemical aspects of medicines. However, during our studies, the chemical aspects of medicines were mostly focused on the analytical aspects. Around that time, Piet Wigerinck, former CSO of Galapagos, who graduated one year before me convinced me to have a talk with his supervisor, Prof. Piet Herdewijn. Piet Herdewijn was a young professor starting up his group in medicinal chemistry and he could easily convince me to join his group. In fact, I was his second PhD student.

Where and when did you obtain your PhD diploma?

After four years of PhD at the Rega Institute of KULeuven in Belgium, I obtained my diploma in 1992 with Prof. Piet Herdewijn as supervisor. The Rega Institute is best known for its research on infectious diseases. That period was marked by the HIV/AIDS pandemic and the discovery of the very first nucleoside and non-nucleoside reverse transcriptase inhibitors. The medicinal chemistry group collaborated intensively with the virology group lead by Prof. Erik De Clercq, and so this was a highly interesting and stimulating environment for me. The first paper I co-authored was published in Journal of Medicinal Chemistry in 1990 on the synthesis and anti-HIV activity of 2’,3’-dideoxyribo-5-chloropyrimidine analogues. This is more than thirty years ago. Time flies.

What was the topic of your PhD project?

The period of my PhD was also the start of chemically modified antisense oligonucleotides and the early days of automated DNA synthesis. We started exploiting the extensive knowledge of nucleoside chemistry available in the group to synthesize sugar-modified DNA analogues. I synthesized several hexopyranosyl nucleoside analogues that were functionalized for automated oligonucleotide synthesis and studied their properties such as hybridization specificity and enzymatic stability. My PhD thesis was entitled: Synthesis of sugar-modified antisense oligonucleotides. It is rewarding to notice that after 30 years of huge efforts the therapeutic principle of antisense oligonucleotides is finally paying off. At the end of 2016, Nusinersen was approved for the treatment of spinal muscular atrophy (SMA).

An interesting story connected to my PhD topic is that one day my supervisor came into my lab and told me that he heard that competition had increased “a little bit”. Around the same time, the group of Albert Eschenmoser at the ETH in Zurich also started investigating the synthesis of hexose nucleic acids. His purpose was to find why nature had chosen for pentose and not hexose nucleic acids. Finally we published almost together in 1992 our findings.

Where did you have your postdoc position?

After my PhD, I belonged to one of the last classes in Belgium that still had to do military service. Next, I went as a postdoc to the medicinal chemistry research group of Prof. Achiel Haemers at the University of Antwerp, Belgium. Soon, I realized that an international experience would be beneficial and applied in Germany for the prestigious international postdoctoral fellowships of the Alexander Von Humboldt Foundation. I was lucky to be selected and worked for one year under the supervision of Prof. Günther Jung at the University of Tübingen in Germany. This was a very rewarding experience. It was the start of combinatorial chemistry and Günther Jung was translating his experience in solid-phase peptide synthesis to applications in combinatorial chemistry. Four years ago, a large group of his PhD students and Postdocs celebrated his 80th birthday with a big party in Tübingen.

Where are you currently working and what is your current position?

Currently I am full professor of medicinal chemistry at the University of Antwerp in Belgium. Next to that I am also the Dean of the faculty of the university and until the end of 2019 I served the European Federation for Medicinal Chemistry in several roles.

What are your current research interests?

One of the major research lines in my group is the discovery of inhibitors of novel types of regulated cell death (ferroptosis and necroptosis) and their application in different animal disease models. Currently, I am also involved as medicinal chemist in a large collaboration financed by the EU-IMI programme to discover novel drugs to treat infections caused by mycobacteria. We are targeting both multiresistant tuberculosis (RespiriTB) as well as infections caused by non-tuberculous mycobacteria (RespiriNTM). Next to that, I am also interested in applications of biorthogonal chemistry for bioimaging and irreversible serine protease inhibitors as chemical tool compounds.

How would you explain what your research area is to non-scientists?

That is a very good point. Science communication to the general public that is paying for our research is extremely important. I indeed often get the question from non-scientists what I am doing the whole day. I usually start by explaining that a university professor has two main tasks: teaching and scientific research. And I add that because of that we don’t have as much holidays as the students. I try to explain that medicinal chemistry deals with the chemistry of medicines and that we make novel molecules that eventually one day can become a drug. The general public also needs to understand that discovering new drugs is a very time- and labour intensive process, but that even small steps that learn us what is the relation between the chemical structure and the therapeutic activity, how a molecule works at the molecular level and how this can influence a disease is important for the field. Nowadays, people more easily understand what Covid-19 is and how detrimental an infectious disease can be. They see the importance of having treatment and prevention options and the need to prepare for a next pandemic. I try to explain them that resistance to existing antibiotics is becoming a major threat and that untreatable bacterial infections is one of the next big challenges.

What do you like best about your work?

In medicinal chemistry, you design and create something new for the benefit of human health. This is in contrast to many other scientific disciplines where you analyse already existing things. I still remember the excitement during my PhD when you synthesize your first molecule that until then never existed on earth before.

What kind of tasks does your work involve?

Currently I am not working in the lab anymore. Next to teaching, an important task is to find money for research by writing national and international grant applications. Successful execution of these research projects is only possible by recruiting highly talented PhD students and postdocs and then guide them towards the research goals. More and more, research is done in multidisciplinary consortia so collaborative skills and networking are highly important as well. As a dean of the faculty, I am furthermore responsible for research policy, personnel and students, and administration. Luckily the latter is limited because I am fortunate to have a very efficient dean’s office. By far the most important task as a dean is to attract bright and motivated young professors.

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

It is difficult to name one. During my PhD we were among the first to incorporate sugar-modified nucleosides into oligonucleotides. As a young professor we pioneered the field of DPP4 inhibitors, which is now a well validated target with several inhibitors on the market as antidiabetic medicines. More recently we published several cell death inhibitors, among which the most potent ferroptosis inhibitors with interesting properties in in vivo disease models. I also felt very honoured to have served the European Federation for Medicinal Chemistry (EFMC) as an executive board member for 11 years, being the president from 2015 until the end of 2017.

Which of your papers are you most proud of and why?

One of my first papers. Augustyns, K. et al. Incorporation of Hexose Nucleoside Analogues Into Oligonucleotides - Synthesis, Base-Pairing Properties and Enzymatic Stability. Nucleic Acids Research 1992, 20, 4711-4716.

How many PhD students and postdocs do you currently supervise? Are you currently looking for a new PhD student or a postdoc?

I am the head of the research group of Medicinal Chemistry at the University of Antwerp (UAMC) that consists of around 25 researchers. I am directly supervising 3 PhD students and 9 postdocs. Currently we are not recruiting, but we had several open positions in the last two years.

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

Of course you should have an excellent knowledge of organic and medicinal chemistry, but even more important is passion for science, ambition and the desire to obtain as much experience as you can through international mobility.

What was your first EFMC experience?

My first EFMC experience must have been as a young postdoc at the International Symposium on Medicinal Chemistry (EFMC-ISMC) in 1994 in Paris. I still remember this as an overwhelming and enthusing experience. As a young scientist I had never imagined to be one day also on stage in front of such a large group of medicinal chemists. In 2002 we decided to restart the Medicinal and Bioorganic Chemistry Division of the Royal Flemish Chemical Society (KVCV). One of the first things we did was to contact Edmond Differding, who was at that time the president of the Medicinal Chemistry Division of SRC, the chemical society of the French speaking part of Belgium. He stimulated us to apply for EFMC membership and in 2004 at the council meeting we were approved and I became EFMC council member. In 2009, when Gerhard Ecker became EFMC President, he asked me to apply for Secretary. That was the start of a 11-year long exciting journey in the executive committee of EFMC with among others the organisation of EFMC-ISMC in 2010 in Brussels and the Frontiers in Medicinal Chemistry symposium in 2015 in Antwerp.

What are your recommendations for a book, podcast, website, blog, YouTube channel or film?

“Breaking Bad”, although I do not recommend anyone to perform the chemistry that Walter White is doing.

Which scientist do you admire the most and why?

Paul Janssen, one of the pioneers of medicinal chemistry and drug discovery. He really brought our field to where we are now and he was and still is an inspiration to many scientists in Belgium and around the world.

Have you experienced any unfair situations during your scientific career?

No. On the contrary, I am very grateful for all the chances that I got and I am most thankful to all my collaborators

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

The challenges in the field of infectious diseases are enormous. Not only we need more and better antivirals but we also badly need novel antibiotics to treat infections caused by multiresistant bacteria.

How do you see the future role of EFMC?

As a scientific federation EFMC has to bring people together around excellent science. In a scientific discipline such as ours that is highly dependent on multidisciplinary collaborations this will always remain an important objective for the future of medicinal chemistry and chemical biology.

During this process, two fundamental changes were determined to be important for the field. First, it was contemplated whether the field of medicinal chemistry in Denmark had more in common with the field of chemistry and, secondly, it was decided that activities in chemical biology are sufficiently related that this area should be included in a new constellation as well. As a result of these considerations, the Danish Society for Medicinal Chemistry and Chemical Biology was founded in 2017 with a board of people representing the largest universities in the country as well as members from industry.

The new society was accepted as a division under the Danish Chemical Society and became the Danish national society member of the EFMC. In this regard, one of the society’s annual activities is organizing a young investigator symposium to select the Danish participant in the EFMC Young Medicinal Chemist’s Symposium.

Interestingly, the decision to include chemical biology in this Danish society turned out to align perfectly with the recent developments within the EFMC. For additional thoughts regarding the chemical biology–medicinal chemistry continuum, please see ChemBioChem, 2021, 22, 2823.

Inhibition of Proprotein Convertase Subtilisin/Kexin type-9 (PCSK9) improves cardiovascular outcomes in patients requiring additional low-density lipoprotein cholesterol reduction on top of statins, but there has been limited uptake of the two commercialized PCSK9 antibody inhibitors due in part to cost and route of administration. The protein-protein interaction between PCSK9 and the low-density lipoprotein receptor which is targeted by these therapies is a large, flat surface, which has made the discovery of orally-bioavailable small molecule inhibitors highly challenging.

This talk will introduce the use of macrocyclic peptides to interrupt such protein-protein interactions and describe the discovery and early chemistry development of such a PCSK9 inhibitor.

Register for free here: https://us06web.zoom.us/webinar/register/WN_Domf-mL5Tg-E3LyD3pr0Fg

#GDCh (MedChem Division), #NextGenMedChem.

The international symposium will focus on current developments, novel approaches and cutting-edge technologies in the field of medicinal chemistry and drug research with sessions on: Non-Mainstream Chemotypes, Chemical Epigenetics, First Disclosures & Case Studies, Next Generation Drugs, Macrocycles, AI – Retrosynthesis and Automation, Medicinal Chemistry and Target Highlights, Young Investigators.

The scientific program will include lectures, and poster presentations. It is the goal of the organisers to make this meeting an event of scientific excellence, attractive to both industrial and academic scientists in Medicinal Chemistry, Chemical Biology, and related fields of research.

More information and registration available here.

5^th RSC / DMDG / DMG New Perspectives in DMPK
22^nd and 23^rd February 2022, Liverpool, UK   
Last chance to register

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

Fragments VIII:  8^th RSC-BMCS Fragment-based Drug Discovery meeting
27^thand 28^th March 2022, Churchill College, Cambridge
Delegate Registration and Exhibitor/Sponsor registration is now open

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

Synopsis:  The aim of the meeting is 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. Over three-quarters of the presentations will be focused on case studies

33^rd Medicinal Chemistry in Eastern England (Hatfield symposium)
28^th April 2022, The Fielder Centre, Hatfield, UK

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

Synopsis:  Known colloquially as the "Hatfield MedChem" meeting, this a highly successful, long-standing, one-day meeting which 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 from the forefront of drug discovery of relevance to medicinal chemists