17th EFMC SHORT COURSE – ACCESS TO THE RECORDED VERSION
The 17th EFMC Short Course on Medicinal Chemistry is fully booked but following high demand, the course will be recorded, and the replays will be made available to interested researchers as of May 10 for a period of three months.
The virtual registration will be 1.000 EUR and includes on-demand access to the recordings of the course, as well as all the course materials in electronic format.
The course will introduce small molecule protein degraders, including PROTACs and molecular glues, and give a detailed overview of the novel technologies used to characterise protein degradation biophysically and in living cells.
More information and registration on www.efmcshortcourses.org.
CALL FOR VOLUNTEERS: JOIN THE EFMC-YSN COMMUNICATION TEAM!
Are you a social media lover with a passion for science? Do you want to make connections and find new opportunities in medicinal chemistry and chemical biology? The EFMC Young Scientists Network (YSN) is looking for contributors like you!
The EFMC Young Scientists Network (YSN) is seeking volunteers to help us create engaging and informative content that will captivate and inspire others. As a volunteer, you will contribute to communicate on our activities such as networking, training, support to young scientists, events, and meetings.
If you have experience with writing on Wikipedia, we would love to hear from you! Our network is looking for skilled writers who can help us create and update articles related to the EFMC and correlated fields.
So why wait? Join EFMC-YSN today and start building a strong network that will help you thrive in your early career. Contact us at firstname.lastname@example.org to learn more about volunteering with EFMC-YSN.
The “literature spotlight” section of the newsletter will bring you a summary of recently published research in a concise and accessible way. Multiple thematics from different journals will be highlighted thanks to the valuable contribution of members of the EFMC working groups.
This contribution will focus on the recently published article on “Genetic Encoding of a Photocaged Histidine for Light-Control of Protein Activity” by Jenny W. Cheung, William D. Kinney, Joshua S. Wesalo, Megan Reed, Eve M. Nicholson, Prof. Alexander Deiters, Prof. T. Ashton Cropp, published in ChemBioChem.
Photocaged residues allow the control of enzyme activity with light. In this study, Cheung et al. introduced a photocaged histidine to a blue fluorescent protein and a chloramphenicol transferase. The histidine residue was linked to a photosensitive o-nitrobenzyl group which can be cleaved using 365''.chr('8197').''nm light. A similar modification was previously described to work with cysteine, tyrosine and lysine. Here, the authors wanted to study the decaging properties of o-nitrobenzyl group from histidine and if the modification can be included in the genetic code.
To get the cells produce the photocaged histidine containing proteins, the team needed to first engineer pyrrolysl-tRNA synthetase to accept the modified histidine as a substrate. They ended up creating an unique variant N311G/C313V/V366K which displayed high specificity towards the photocaged histidine and very little background activity in the absence of the unnatural amino acid. Then they genetically engineered a blue fluorescent protein and a chloramphenicol transferase to display that the photocaged histidine at the active site can be used to control enzyme activity.
In summary, the authors showed that it is possible to include a photocaged histidine containing proteins into both bacterial and mammalian cells. The discovered pyrrolysl-tRNA synthetase can be further optimized to include other unnatural amino acids into the produced proteins. Irradiation of the proteins containing these resides resulted in an activation. The used caging group has some limitations (365nm wavelength has low tissue permeability and requires long irradiation times) which the authors hope will get solved with alternative caging groups.
Read the article
REPORT OF THE EFMC SESSION AT ACS SPRING 2023
The 2023 Spring edition of the biannual national meeting of the American Chemical Society (ACS) was held from March 26–30 at the Indiana Convention Center, located in the heart of the 12th largest city in the U.S., the Indiana state capital, Indianapolis. Since August 2015, where a Memorandum of Understanding has been signed between the Medicinal Chemistry Division (ACS MEDI) and the EFMC, an exchange of sessions has been organized, and the EFMC was thrilled to set another milestone of this collaboration.
Being the fourth ACS’s hybrid event (a series started in 2021 during the COVID19 pandemic), the 265th general ACS meeting was attended by over 12,600 registered participants (as of March 29), 85% of which traveled to Indianapolis, while 15% attended virtually. The theme of the meeting was "Crossroads of Chemistry" and the impressive scientific program offered 9,230 oral and poster presentations, covering as usual the complete field of chemistry, and included many fantastic sessions, in particular those of the ACS MEDI.
The EFMC session on ‘Emerging and re-emerging warheads for targeted covalent inhibitors: applications in medicinal chemistry and chemical biology’ was quite a success. In an almost fully packed Sagamore Ballroom 2 (320 people theater capacity), the attendees extremely appreciated the high level and quality of the presentations and contributed to the session with lots of questions and comments.
The session was chaired by the EFMC EC member and Secretary Gianluca Sbardella, who gave the opening and closing remarks and introduced the EFMC and its activities (including MedChemBioWatch) aimed to promote medicinal chemistry and chemical biology.
The session continued with three outstanding keynotes lectures by Stefan Laufer (University of Tübingen, Germany and member of the EFMC Best Practices in Medicinal Chemistry WG), who discussed the design of orthosteric and allosteric isoindolinone-derived pocket-spanning epidermal growth factor receptor (EGFR) inhibitors and gave insights into the essential SARs for the occupation of the two binding sites with one ligand, Kay Brummond (University of Pittsburgh, Dietrich School of Arts and Sciences, USA), who described the synthesis and the thiol reactivity of α-Methylene−γ-lactones and α-methylene-γ-lactams as valuable warheads in the rational design of covalent inhibitors, and Birgit Wilding (Boehringer Ingelheim RCV GmbH und Co KG, Austria), who reported the structure-based design and lead optimization efforts which resulted in new, orally bioavailable covalent inhibitors that show excellent potency on human epidermal growth factor receptor 2 (HER2), including hard-to-hit mutations.
After a short break, other two terrific keynote lectures were given by Robert Pulz (Novartis Pharma AG, Switzerland), who discussed the design, characterization, and medicinal chemistry optimization of a series of highly selective covalent Bruton’s Tyrosine Kinase (BTK) inhibitors stabilizing an inactive confirmation of BTK resulting in the identification of remibrutinib as a highly potent inhibitor with a best-in-class selectivity profile, and Sara Buhrlage (Dana-Farber Cancer Institute, USA), who presented a multidisciplinary platform established by her lab for discovery, optimization and rigorous characterization of deubiquitinases (DUBs) inhibitors and present her work using first-in-class probes to study DUB biology in both biased and unbiased fashion.
The EFMC thanks the speakers for their inspiring talks and the ACS MEDI, in particular Maria-Jesus Blanco (Atavistik Bio and ACS MEDI Division Chair), Amjad Ali (Merck and ACS MEDI Division Program Chair), and Daniel Harki (University of Minnesota and ACS MEDI observer delegate to the EFMC Council) for the great job done in the symposium organization and for the warm and excellent treatment they provided. The collaboration between EFMC and ACS MEDI will be soon further strengthened by the co-organized Joint Symposium ACSMEDI-EFMC Medicinal Chemistry Frontiers 2023 that will be held in Boston, MA (USA) June 10-13, 2023, and after this an ACS MEDI session is planned to be held in the EFMC-ISMC 2024 Symposium in Rome.
Report by Gianluca Sbardella (University of Salerno, Italy)
From left to right : Robert Pulz (KN lecturer), Birgit Wilding (KN lecturer), Gianluca Sbardella (EFMC EC Secretary and session chair), Sara Buhrlage (KN lecturer), Kay Brummond (KN lecturer), Christa Müller (EFMC EC member), Rui Moreira (EFMC President), Stefan Laufer (KN lecturer).
From left to right: Birgit Wilding (KN lecturer), Rui Moreira (EFMC President), Maria-Jesus Blanco (ACS MEDI Division Chair), Gianluca Sbardella (EFMC EC Secretary and session chair), Stefan Laufer (KN lecturer), Kay Brummond (KN lecturer), Robert Pulz (KN lecturer).
CELEBRATE THE 10 YEARS OF THE EFMC YOUNG MEDICINAL CHEMISTS’ SYMPOSIUM (EFMC-YMCS) WITH US!
The 10th edition of the EFMC Young Medicinal Chemists' Symposium will be held in Zagreb, Croatia on September 7-8, 2023 and will be organised by the European Federation for Medicinal Chemistry and Chemical Biology (EFMC) and the EFMC Young Scientists Network (YSN).
This short symposium aims to create and maintain a network of young European investigators, encouraging them to share their research with their peers and promoting competition and excellence in a relaxed atmosphere.
Register and celebrate with us!
Register before the early bird deadline and share your scientific achievements! Approximately 20 flash presentations will be selected and several prizes, both for flash presentations and posters, will be awarded during the symposium.
- for Flash Poster Presentations: May 3, 2023
- for Posters: June 8, 2023
The Programme will include keynote lectures by inspiring leaders in the field, oral communications by invited prize winners from national young medicinal chemist meetings in Europe, prize lectures from winner of the EFMC-YSN PhD Prize and Symeres PhD Prize for Excellence in Chemistry in Life Sciences Research and flash poster presentations. EFMC-YMCS will also feature a poster session, an exhibition, a series of soft-skill training, and networking activities provided by the EFMC Young Scientists Network.
Do not miss the opportunity to celebrate a decade of fruitful exchanges and high-quality science with us!
THE LATEST EFMC REVIEW ON THE TRENDS THAT DRIVE INNOVATION IN DRUG DISCOVERY – NOW FREE TO READ FOR 3 MONTHS
Recently published! The latest EFMC review on the trends that drive innovation in drug discovery is now freely accessible for a period of three months!
A wealth of opportunities: Novel tools for chemical biology including chemical inducers of proximity, designer probes or RNA-targeting agents enable innovative tactics for therapeutic approaches. This article explores recent developments combining the power of medicinal chemistry and chemical biology, highlighting their extraordinary potential to address sophisticated biological questions and manipulate complex biological pathways to develop novel therapies.
#IAMAMEDICINALCHEMIST BECOMES MEDCHEMBIOCONVERSATIONS
The #Iamamedicinalchemist series has been created to help promote Medicinal Chemistry, Chemical Biology and related fields in Europe and around the globe, and inspire future scientists in sharing stories and views of researchers working in the fields.
True to the EFMC values of inclusive representation of all its members, it showcased not only Medicinal Chemists but also Chemical Biologists, Computational Chemists, and associated researchers to the point that the original name no longer felt relevant.
With MedChemBioConversations, the EFMC wants to mirror the diverse nature of the interviews but also embrace a new format. Soon, future interviews will no longer be exclusively transcript - but will also be presented as short video capsules or podcasts.
GET TO KNOW GYORGY KESERU (RESEARCH CENTRE FOR NATURAL SCIENCES, HUNGARY)
In this edition, our MedChemBioConversations is with Dr Gyorgy Keseru from the Research Centre for Natural Sciences, Hungary.
Get to know him better by reading the interview below:
How did you get interested in Medicinal Chemistry?
I grew up in a pharmacist’s family, my father, mother and my sister are all pharmacists. Since at that time I was less interested in biology, I focused on chemistry and obtained my MSc in Chemical Engineering. During my undergraduate years I joined the research group of Prof Nógrádi on natural products chemistry as a research student. After completing my thesis in Karlsruhe, Germany, I continued natural product synthesis that was extended by structural and biological studies. Natural products, ethnomedicine and the film, Medicine Man starring Sean Conory inspired me towards Medicinal Chemistry.
I learned cheminformatics and drug design at Budapest during my postdoc years and then joined Sanofi heading a chemistry research lab in 1996. I then moved to Gedeon Richter where I spent 14 years before moving back to academia in 2013.
Where are you currently working and what is your current position?
Now I am working in the Research Center for Natural Sciences and heading the Medicinal Chemistry Research Group. My group is focusing on two therapeutic areas, one is CNS that is coming from my industry experience and the other is oncology that is one of the key areas in the Research Center.
We are heavily involved in fragment based drug discovery and more recently, we combined FBDD with approaches using covalent mechanism of action. In addition to FBDD programs, we are interested in developing new methodologies with covalent fragments including new warhead chemistries, novel labelling techniques, screening approaches and chemoproteomics applications.
We develop screening libraries including pharmacophore optimized fragment libraries and covalent fragment libraries. These are typically screened against our targets of interest and next we characterize the hits before designing, synthesizing and testing further, improved molecules as follow-up. Recently we opened towards challenging targets including transcription factors, intrinsically disordered proteins and COVID targets, but even for more complex systems such as antibodies and proteasomes.
How would you explain what your research area is to non-scientists?
Basically, our objective is to build drugs from small building blocks within the suitable pockets of the target protein. The most challenging part of this is finding the first one since the individual building blocks bind less tightly to the protein target. Therefore, we recently extended our research to those starting points that can be sticked to the pocket due to their reactivity.
What do you like best about your work?
We are working in teams. Research teams include design and synthesis people and also colleagues more interested in analytics or biological experiments. In addition, we have many students at different levels from BSc to PhD. This diversity makes the atmosphere of our community very stimulating since our common goals and the different expertise create an exciting working environment.
How many PhD students and postdocs do you currently supervise?
There are 7 PhD students and 5 postdocs in my lab.
Are you currently looking for a new PhD student or a postdoc?
We were recently awarded a grant to create our National Laboratory on Drug Discovery and Development, and we are actively looking forward to talented candidates to turn this dream into reality in the coming years.
How would you describe yourself as a supervisor?
Having about 40 people in my group, daily supervision is part delegated, however, I am always available for discussing the hot topics identified in our research team. Communication between the teams is facilitated by biweekly group meetings which is when we review the progress together.
Which of your papers are you most proud of and why?
Working in drug discovery and development I am extremely proud of contributing to the discovery of cariprazine, a third generation antipsychotics that showed efficacy in bipolar disorder and depression. The drug was approved worldwide and reached blockbuster status last year. During the pandemic, I was involved in the development of a generic COVID drug that received emergency use authorization in Hungary and contributed to our national COVID efforts.
In science terms, our contribution to binding thermodynamics, fragment based approaches and development of optimization metrics might be notable. I am very proud of the four Nature Reviews Drug Discovery papers we published on compound quality and optimization strategies together with industry colleagues. More recently, we have two methodology papers, one on fluorescent microscopy and the other on designing effective fragment libraries, both published in Nature Communications.
What are the features of a successful PhD student or postdoc?
I think successful students have an exceptional interest on the topic, they are strongly focused and most importantly, highly motivated and fully committed to research.
What advice would you give to someone who wants to know more about your field?
I truly believe in personal contacts. Please contact me via email and I would be happy to provide more information on our work. If there is a general interest to the overall field, I would suggest to attend the relevant meetings.
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
I would suggest the book “The Practice of Medicinal Chemistry” by Camille Wermuth that is a good introduction to medicinal chemistry, as general reading. I consider drug discovery case studies specifically important. The published success stories provide valuable experience for practitioners.
I mention here the book series of “Successful drug discovery” and the Annual Reports in Medicinal Chemistry. Nature Reviews Drug Discovery publishes fresh analysis and review papers focusing on the current trends.
I also enjoy Derek Lowe’s “In the Pipeline” and Dan Erlanson’s “Practical Fragments” blogs.
AWARDEES SELECTED FOR THE JOINT YSN-YMCC GRANT TO ATTEND ACSMEDI|EFMC MEDICINAL CHEMISTRY FRONTIERS
We proudly announce the names of the first awardees of the joint grant funded by the EFMC Young Scientists Network (YSN) and the ACSMEDI Young Medicinal Chemists Committee (YMCC).
- Dr Aleša Bricelj, University of Ljubljana, Slovenia
- Dr Andreas Luttens, Uppsala University, Sweden
Congratulations to both for their outstanding application!
Each grant of up to 1500€ will be used to cover registration, economy flight and up to 3-nights accommodation to attend the upcoming edition of the ACSMEDI|EFMC Medicinal Chemistry Frontiers will take place in Boston, United States on June 10-13, 2023. Each one of them will present their research at the conference with a Poster and will be invited to submit an abstract for Oral Communication.
Aleša Bricelj obtained her master’s degree in pharmacy at the Faculty of Pharmacy, University in Ljubljana in 2019. She is currently a fourth-year PhD student under the supervision of Assist. Prof. Izidor Sosic and Prof. Marko Anderluh at the Faculty of Pharmacy, University of Ljubljana. Her research focuses on utilising PROTACs for targeted protein degradation of various proteins involved in malignancies.
||Andreas Luttens has received his master’s degree in molecular design in Chemistry from Ghent University, Belgium. He is currently pursuing a Ph.D. in Molecular Life Sciences at Uppsala University, Sweden. Andreas joined the lab of Jens Carlsson in 2017 and works on novel strategies to navigate vast chemical spaces using virtual screening
#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 April 26 by Dr Benjamin Horning (Vividion Therapeutics).
The topic of the webinar will be “Industrialized Chemoproteomics Enables the Discovery of Allosteric Modulators of Janus Kinase 1 and Cereblon Targeting Novel Sites”
Interest in covalent inhibitors has seen a resurgence in recent years, owing in large part to proteomics technology to assess selectivity and de-risk off-target concerns. We have utilized our proteomics platform to guide the development of a screening library containing small molecules armed with covalent reactive groups. From these efforts we have discovered inhibitors of Janus kinase 1 (JAK1) that potently and selectively inhibit JAK1 mediated cytokine signaling through a novel allosteric pocket on the pseudokinase domain, distinct from the pocket bound by recent clinical stage inhibitors of the related kinase Tyk2. We demonstrate that our inhibitors function via inhibiting trans-phosphorylation of JAK1 via its heterodimeric JAK family member, a key step in the signaling cascade. These covalent, allosteric JAK1 inhibitors avoid the selectivity issues common to traditional kinase inhibitors, which bind to highly conserved kinase active sites. Moreover, since the target cysteine in JAK1 is not highly conserved, they have the potential to avoid potential clinical safety issues associated with inhibiting off targets such as JAK2. In addition, we have discovered a novel pocket on the E3 ligase Cereblon that can be targeted by covalent molecules. Binding to this pocket allosterically prevents imide binding, and the allosteric relationship between these two sites can be utilized to monitor imide binding to Cereblon in bifunctional molecules.
Register for free here.
#GDCh (MedChem Division), #NextGenMedChem.
NEWS FROM THE BIOLOGICAL AND MEDICINAL CHEMISTRY SECTOR (BMCS) OF THE ROYAL SOCIETY OF CHEMISTRY (RSC)
The BMCS is pleased to open nomination calls for the Capps Green Zomaya Memorial Awards 2024 and the BMCS Hall of Fame and Medal 2023, as well as some upcoming events.
- 10th SCI/RSC Kinase Symposium on Inhibitor Design
- 3rd Synthesis in Drug Discovery and Development
- 3rd RSC Anglo-Nordic Medicinal Chemistry Symposium
Capps Green Zomaya Memorial Award 2024
The Biological and Medicinal Chemistry Sector of the Royal Society of Chemistry is pleased to invite nominations for the eleventh Capps Green Zomaya Memorial Award in medicinal or computational chemistry. The Award will be given to the individual judged to have made an important contribution to the discovery or development of new medicines. Nominations are invited for candidates, up to the age of 40, working in UK or international laboratories (candidates over the age of 40, who have taken career breaks, will be considered). A Royal Society of Chemistry commemorative medal and certificate will be awarded to accompany the prize of £2,000
Nominations should be submitted no later than 31 October 2023 to: RSC-BMCS Secretariat, Hg3 Conferences Ltd, email: email@example.com
For further details, please access the activities link on www.rsc.org/bmcs
BMCS Hall of Fame and Medal 2023 – Call for nominations.
The BMCS is pleased to announce the 2023 call for nominations for its Hall of Fame and associated medal which recognises chemists for outstanding, sustained, significant contributions to any area of interest to the BMCS, including medicinal chemistry, agriscience, bio-organic chemistry, and chemical biology. Independent nominations may be submitted by e-mail outlining the justification and including the nominee’s CV and publication list. Additional independent letters of support to reinforce the nomination are strongly encouraged. Nominees should be resident in the UK or continental Europe, or have spent a considerable proportion of their career there. There is no requirement to be an RSC or BMCS member. There are no age restrictions, and nominees may have an academic or industrial background. Nominations should be submitted by the end of September 2023 and the outcome will be communicated to nominators and nominees by mid-December 2023. Inductees will receive a medal and certificate, and will be invited to give a plenary lecture at an appropriate BMCS organized conference.
Independent nominations should be sent to the RSC-BMCS Secretariat, Hg3 Conferences Ltd, email: firstname.lastname@example.org from 1 March to 30 September 2023.
For the full list of requirements and terms and conditions, please see the guidance notes above
10th SCI/RSC Kinase Symposium on Inhibitor Design
9thand 10th May 2023, SCI, London, UK
Synopsis: With more than 70 FDA-approved small molecules, the field of kinase inhibition continues to attract significant investment from the drug discovery and development community. The 10th SCI/RSC symposium on kinases will encompass plenary lectures on emergent topics and case studies of ongoing programmes as well as successful past programmes. A range of topics including new screening approaches, brain penetrant kinase inhibitors, induced protein degradation, allosteric inhibitors and kinase inhibition for immuno-oncology will be covered, along with views and perspectives on the future of kinase inhibitor research
3rd Synthesis in Drug Discovery and Development
23rd – 24th May 2023, Virtual
Synopsis: Synthesis is at the heart of drug discovery and development. The industry has increasingly demanded higher quality clinical candidates and has sought to exploit less druggable biological targets. Densely functionalised small molecules with a high degree of synthetic complexity are often the result of these demands. Successful programmes therefore require the application of innovative synthesis in all stages of discovery and development. The medicinal chemist’s toolbox is also enhanced by the introduction of novel bioisosteres, often made available only through the application of new synthetic methods. This symposium aimed to celebrate the crucial role of synthesis in the success of drug discovery and development
3rd RSC Anglo-Nordic Medicinal Chemistry Symposium
13th-16th June 2023, Hotel Comwell Borupgaard, Snekkersten, Denmark
Deadline for poster abstracts is 4th May 2023
Synopsis: Organised with Nordic affiliations, the scientific programme will feature themed lectures, focusing on medicinal chemistry and related technologies and disciplines across a range of drug targets and modalities. A distinguishing feature of this symposium is the collegiate style which encourages an atmosphere of information sharing and learning.
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EFMC ORGANISED EVENTS
May 25, 2023
April 23-26, 2023
Oegstgeest, The Netherlands
17th EFMC Short Course on Medicinal Chemistry
June 10-13, 2023
Boston, United States
ACSMEDI-EFMC Medicinal Chemistry Frontiers
September 3-7, 2023
IX International Symposium on Advances in Synthetic and Medicinal Chemistry (EFMC-ASMC)
September 7-8, 2023
10th EFMC Young Medicinal Chemists' Symposium (EFMC-YMCS)
November 16-18, 2023
EFMC International Symposium on Chemical Biology (EFMC-ISCB)
EFMC SPONSORED EVENTS
April 27, 2023
Hatfield, United Kingdom
34th Medicinal Chemistry in Eastern England (Hatfield symposium)
May 15-16, 2023
International Helmholtz Drug Discovery Conference – HDDC2023
May 21-24, 2023
IX European Workshop in Drug Synthesis (EWDSy)
May 23-24, 2023
3rd Synthesis in Drug Discovery and Development
June 13-16, 2023
3rd RSC BMCS Anglo-Nordic MedChem
July 5-7, 2023
September 17-20, 2023
National Meeting on Medicinal Chemistry (NMMC28)
December 7, 2023
Oxford, United Kingdom
RSC-BMCS Postgraduate Symposium XVII
June 19-21, 2023
Santiago de Compostela, Spain
VIII SEQT Summer School
July 2-6, 2023
European School of Medicinal Chemistry (ESMEC)
September 10-15, 2023
Vienna Summer School Drug Design
PhD candidate in Chemical Biology, Max Planck Institute of Molecular Physiology, GERMANY
Postdoctoral Position in Radiopharmaceutical Development and Preclinical Imaging, University Hospital Basel, SWITZERLAND
Roche Postdoctoral Fellow (RPF) in Medicinal Chemistry/Super-Resolution Microscopy, F. Hoffmann-La Roche, SWITZERLAND
Applications Scientist, Schrödinger, FRANCE