EFMC-WuXi AppTec AWARD FOR EXCELLENCE IN CHEMICAL BIOLOGY – CALL FOR NOMINATION
The "EFMC-WuXi AppTec Award for Excellence in Chemical Biology" will recognise outstanding research in the field of chemical biology as defined by EFMC in The Chemical Biology-Medicinal Chemistry Continuum: EFMC’s Vision, ChemBioChem 2021, 22, 2823– 2825.
The Award will be presented biennially and will consist of a diploma, € 7.500, and an invitation to present a lecture at an EFMC-ISCB symposium.
The award shall be open to any scientist whose career does not exceed 20 years after PhD on January 1st of the year during which the award is to be presented, and whose accomplishments have not yet been honoured by other EFMC awards.
The award will be conferred on the occasion of the European Federation for Medicinal chemistry and Chemical Biology International Symposium on Chemical Biology (EFMC-ISCB).The EFMC-ISCB 2023 will be held in Basel, Switzerland on November 16-18, 2023.
Deadline for submission: January 31, 2023
More information on The EFMC-WuXi AppTec Award for Excellence in Chemical Biology.
EFMC PRIZES 2023 – CALL FOR NOMINATION
To acknowledge and recognise outstanding young medicinal chemists and chemical biologists (≤ 12 years after PhD) working in European industry and academia, the EFMC established the "EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Industry" and the "EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Academia".
These two prizes are given annually and consist of a diploma, 1.000€ and an invitation for a short presentation at an EFMC symposium.
For the 2023 edition, the prize-winners will be invited to give an oral communications at the IX EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry (EFMC-ASMC 2023), scheduled to take place in Zagreb, Croatia on September 3-7, 2023. Two additional nominees will also be identified and acknowledged as most meritorious runners-up.
Deadline for nominations is January 31, 2023.
EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Industry
Nominations should be written by the candidate’s supervisor and consist of:
- a letter by the supervisor.
- a brief candidate CV.
- an abstract of the potential oral presentation.
EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Academia
Applications should consist of:
- a one-page letter by the candidate, including a short rationale for their application.
- one page with five key publications.
- a brief candidate CV.
- an abstract of the potential oral presentation.
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 “Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI-001 in in''.chr('8197').''vitro Models of Prostate Cancer Drug Resistance” by R. C. Bizga Nicolescu et al. published in ChemMedChem.
Heterobifunctional molecules such as PROTACs and multitarget compounds have emerged as promising modalities against challenging targets and diseases, and particularly promising for cancer treatment. In this article, R. C. Bizga Nicolescu et al. develop conjugate molecules comprising two androgen receptor (AR) inhibitors to treat metastatic pancreatic cancer (PCa).
Patients with PCa that develop metastasis are often treated with androgen-deprivation therapy, but often progress to a more advanced and often incurable stage known as Castration-Resistant Prostate Cancer (CRPC). They then receive second generation AR inhibitors such as enzalutamide or other steroidal and non-steroidal anti-androgens. However, development of resistance to these inhibitors is common, which often occurs through the formation of AR variants (AR-Vs) that lack the AR ligand-binding domain (LBD) where enzalutamide binds. To address this limitation, another class of inhibitors has been developed to target the alternative N-terminal domain (NTD); these contain a bisphenol A core structure and are known as EPI analogues. Even though EPI analogues such as EPI-001 can inhibit AR-Vs lacking the LBD, they display poor pharmacokinetic properties and have low potency.
To circumvent the limitations of the known AR inhibitors, R. C. Bizga Nicolescu et al. developed hybrid compounds that simultaneously target both sites of the AR, i.e., LBD and NTD. The authors prepared five analogues containing enzalutamide and EPI-001 covalently linked with different triazole-PEG linkers. In C4-2b, a metastatic prostate cancer cell line expressing several AR-Vs, their conjugates displayed up to 53-fold improvement of LC50 compared to the initial inhibitors alone or in combination. On the other hand, smaller effects were observed for some of their molecules in PC-3 cells, which express very low levels of AR-Vs, supporting their AR-dependent toxicity. Their top compound 9b had an LC50 of 1.6 µM in C4-2b cells but >75% viability at 10 µM in PC-3 cells. The authors hypothesise that the enhanced potency of the conjugates, as compared to a combination of the original inhibitors, could be due to an entropic effect, where the linker may be increasing the effective local concentration of the second inhibitor.
The team then proved interaction of some of the compounds with AR. Firstly, 9b inhibited AR-mediated transcriptional activity in a luciferase assay. Secondly, RT-qPCR experiments showed that 9e inhibited expression levels of the KLK3 gene, which is tightly regulated by the AR. In these assays the compounds were found to be less potent than enzalutamide, most likely due to lower membrane permeability.
In conclusion, the authors developed a first-in-class AR inhibitor 9b that circumvents some of the limitations of current clinical drugs for aggressive stages of PCa.
Bizga Nicolescu, R. C., Maylin, Z., Perez Areales, F. J., Iegre, J., Pandha, H., Asim, M., & Spring, D. R. (2022). Hybrid androgen receptor inhibitors outperform enzalutamide and EPI''.chr('8208').''001 in in vitro models of prostate cancer drug resistance. ChemMedChem. doi:10.1002/cmdc.202200548
EFMC GRANTS 2023 – APPLICATIONS ARE OPEN
EFMC is funding grants for EFMC organised events with the aim to support the participation of young academic scientists.
Upon application, a limited number of grants will be covered by EFMC, corresponding to:
- The full registration fees for EFMC-ISMC, EFMC-ASMC, EFMC-ISCB and ACSMEDI-EFMC Medicinal Chemistry Frontiers
- Up to 50% of the registration fees for the EFMC Short Courses
The following Grant applications for 2023 events are open
Once registered in the grant system, you will receive a confirmation email with your data to access your secured page, and upload the following:
- Cover letter
- Support letter by the supervisor
- Publications' List
- Abstract of the Oral Communication/Poster Presentation (not required for the EFMC Short Course)
Please be informed that following EFMC regulations, only the members of an EFMC National Adhering Organisation will be allowed to apply for the EFMC grants.
EFMC WELCOMES THREE NEW MEMBERS IN THE EXECUTIVE COMMITTEE
Dr Mathilda Bingham (Malvern Panalytical, United Kingdom), Prof. Beatriz De Pascual Teresa (CEU San Pablo University, Spain) and Dr Martin Missbach (Novartis, Switzerland) have been elected by the EFMC Council to become members of the Executive Committee for a period of two years from January 1st, 2023.
We are proud to welcome these three new members into the committee and we look forward to a fruitful collaboration.
They will be joining the current members:
- Prof. Rui Moreira (University of Lisbon, Portugal) – President
- Dr Luc Van Hijfte (Symeres, The Netherlands) – President Elect
- Prof. Gianluca Sbardella (University of Salerno, Italy) – Secretary
- Prof. Christa Müller (University of Bonn, Germany) – Member
EFMC would also like to sincerely thank Dr Yves Auberson (Novartis, Switzerland), Prof. Anders Karlén (Uppsala University, Sweden) and Dr Antoni Torrens (WeLab, Spain) for their contribution as executive committee members for the past years.
EFMC ADVENT CALENDAR – CALL FOR PICTURES
The EFMC Communication Team is actively preparing for the Holiday Season and invites you all to contribute to its Social Media Advent Calendar.
Please share the most festive picture from your lab with us and get showcased on the EFMC Twitter or Instagram account. The most-liked picture by December 24th noon CET will win a 25€ prize and an EFMC GoodieBox.
How to participate?
- Share your picture by PM via Twitter, or
- Tag us from a public account on Twitter (@EuroMedChem) or Instagram (@euromedchem), or
Share your picture and details via email to firstname.lastname@example.org
BEST PRACTICES IN HIT GENERATION
Hit Generation is a crucial step of all drug discovery campaigns that will determine the speed and chance of success of identifying drug candidates. We cover the essential approaches for hit generation and the opportunities and challenges they come with. We then provide guidance on how to validate hits to ensure medicinal chemistry is only performed on compounds and scaffolds that engage the target of interest and have the desired mode of action. Finally, we discuss the design of integrated hit generation strategies that combine several approaches to maximize the chance of identifying high quality starting points.
If you missed the excellent webinars and slide decks by the EFMC Best Practices working group, these can still be accessed on https://www.efmc.info/hit-generation.
GET TO KNOW VANESA NOZAL, CENTRO DE INVESTIGACIONES BIOLÓGICAS MARGARITA SALAS (CIB-CSIC), SPAIN
In this edition, our #Iamamedicinalchemist is Vanesa Nozal for Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Spain. Vanesa was also one of the most meritorious runners-up of the 2023 EFMC-YSN PhD Prize.
Get to know her better by reading our interview below.
How did you get interested in Medicinal Chemistry?
I started to get involved in the field of Medicinal Chemistry while I was studying in Belgium, during the last year of my degree. I had the opportunity to discover how the organic chemistry that I have studied could influence and benefit the society. After synthesizing new antibiotics, I changed to the field of kinases in neurodegenerative diseases which has been the topic of my PhD project. It has been a challenging but rewarding pathway as targeting the CNS is arduous.
Where are you currently working and what is your current position?
After finishing my PhD this last April, I currently work in at CIB CSIC as a postdoctoral fellow, but I am actively searching a postdoctoral position abroad to continue with my academic career. I would like to learn novel techniques like DEL, computational chemistry, DCC or PROTACS to complete my background in kinase inhibitors drug discovery, structural biology, and nanoparticles. Previously we have been trying to develop new drugs for the treatment of amyotrophic lateral sclerosis and other neurodegenerative diseases. I design and synthesize new chemical compounds to target kinases.
What do you like best about your work?
The best part of my job is working with other scientists and being able to directly see how my molecules interfere and change the course of the disease model in cells and in animals. I like the multidisciplinary environment that I have experienced since in my opinion it is the best way to expand your knowledge and your limits. Another positive aspect of being a scientist is the opportunities to meet people from different backgrounds and countries in the multiple symposiums and meetings that we attend.
What do you consider your greatest achievement in your scientific career?
I am very proud of being the most meritorious runner-up for the 2022 EFMC-YSN PhD Prize, I am aware of the great level of other PhD candidates across Europe and this has been a great honour for me. Related to my research, I enjoyed writing the paper related to multitarget compounds for Alzheimer’s disease, which was published in 2021. It was a challenging but exciting project in which I implemented target-guided synthesis. Seeing the final paper published in Angewandte Chemie and the bigger picture of the project after many years was a great reward.
What are the features of a successful PhD student or postdoc?
In my experience, the most important aspect of a successful PhD thesis is being happy with your project and working in a good laboratory, with a healthy atmosphere and a great supervisor. I could not imagine overcoming all the difficult situations that happened during these years without the support of my supervisor and my colleagues. Another aspect that I have enjoyed very much is participating in dissemination activities with other scientists and also with the general public. It helps to see other aspects of your research and make the effort to explain it to someone that is not an expert in science. Finally, I believe that scientists can really make a change so I am usually involved in research associations or federations, because I think that we have to fight for what we consider fair.
What is the most embarrassing thing you have done in the lab while carrying out experiments, e.g. explosions?
During a short stay related to protein crystallography in another CSIC centre, one colleague of mine and I accidentally swopped the crystals that we were analysing in the synchrotron. After three years of research, it was the first time that my colleague was diffracting protein crystals but they were not his crystals but mine…
What are your recommendations for a book, podcast, website, blog, YouTube channel or film?
Related to science and dissemination, I enjoyed very much a Spanish podcast called “Catástrofe Ultravioleta”. They share very interesting stories about scientific and historic discoveries from an innovative point of view. I have, of course, seen all the chapters of the TV series “The BigBang Theory”. It is very funny to see how they picture scientists and the hilarious criticism that they direct towards pharmaceutical companies.
Which scientist do you admire the most and why?
I really admire Marie Curie and her husband Pierre. I think he supported his wife and contributed to the recognition of the success of every woman in science after her. I am a big fan of Rafael Yuste, a Spanish neurobiologist; he is one of the drivers of the BRAIN project. I heard one of his conferences related to neurorights which had a great impact on me.
Which field of medicinal chemistry do you consider the most promising for the future?
I think that DNA-encoded libraries have a promising future, in order to engage the target in the discovery of its own inhibitor and accelerate this process. I also really hope that Medicinal Chemistry would be able to find cures for neurodegenerative diseases such as amyotrophic lateral sclerosis or different dementias. Millions of patients count on us.
NEWS FROM THE FRENCH MEDICINAL CHEMISTRY SOCIETY/SOCIÉTÉ DE CHIMIE THÉRAPEUTIQUE (SCT)
The SCT is happy to announce the 30nd Young Research Fellows Meeting, scheduled to take place in Paris, France on February 1-3, 2023.
This meeting brings together ~300 young European scientists giving them the opportunity to present their most recent results. The topics presented cover all aspects of medicinal chemistry: chemical biology, chemoinformatics, SAR studies, ADMET, imaging, physical chemistry, biolabeling and diagnostic tools, drug vectorization, nanotechnologies, natural products, synthetic methodology, etc.
Registration deadline is December 14, 2023
More information on https://www.sct-asso.fr/yrfm-young-research-fellow-meeting.
#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 December 14 by Prof. Anna K.H. Hirsch (HIPS, Germany).
The topic of the webinar will be “Addressing Unusual Anti-infective Targets”.
The challenges associated with anti-infective drug-discovery programmes can be tackled by combining several established hit-identification strategies with phenotypic antibacterial screening. I will illustrate this approach with a selection of un(der)explored targets. The first is a vitamin transporter from the energy-coupling factor (ECF) class, which is unique to Gram-positive bacteria. Here, we report on the structure-based virtual screening (SBVS), design, synthesis and structure–activity relationships of the first classes of selective, antibacterial inhibitors of the energycoupling factor (ECF) transporters with good in vitro and whole-cell activity and a good in vitro ADMET and in vivo PK profiles. A newly established cell-based uptake assay in Lactobacillus casei greatly facilitated our screening and hit-to-lead optimisation campaign. The second is the β-subunit of the bacterial DNA polymerase III (sliding clamp, DnaN), an attractive antibacterial target. We pursued several hit-identification strategies, including a SBVS campaign, affording novel chemotypes with micromolar affinity and promising antibacterial activity. Mode-of-action studies confirmed DnaN as the molecular target. The new compound displays broad-spectrum antibacterial activity against mycobacteria, Gram-positive and Gram-negative pathogens also against multidrug-resistant bacteria with no cytotoxicity and good in vivo PK profiles. Finally, we succeeded in fragment merging and linking, affording highly selective and potent inhibitors of the extracellular metalloprotease and virulence factor of Pseudomonas aeruginosa, the elastase LasB. Multiparameter optimisation is currently ongoing based on extensive in vitro and ex vivo profiling, including the establishment of complex biological assays. Our approach promises to deliver the urgently needed anti-infective agents featuring both new chemical scaffolds and unprecedented modes of action. Multiparameter optimisation is currently ongoing based on extensive in vitro, wholecell, ex vivo and in vivo profiling, including the establishment of complex biological assays. A particular emphasis will be placed on the lead optimisation of frontrunners for permeation and achieving good lung exposure.
Register for free here: https://us06web.zoom.us/webinar/register/WN_p_pV6AZQT56aeCmzjxiv9Q
#GDCh (MedChem Division), #NextGenMedChem
NEWS FROM THE BIOLOGICAL AND MEDICINAL CHEMISTRY SECTOR (BMCS) OF THE ROYAL SOCIETY OF CHEMISTRY (RSC)
The BMCS is delighted to announce the upcoming events.
- 7th RSC-BMCS / SCI Symposium on Ion Channels as Therapeutic Targets
- 10th SCI/RSC Kinase Symposium on Inhibitor Design
- 3rd Synthesis in Drug Discovery and Development
7th RSC-BMCS / SCI Symposium on Ion Channels as Therapeutic Targets
27th and 28th March 2023, Wellcome Genome Campus, Cambridge
Closing date for poster abstracts is 31st December
Synopsis: Ion channels are important targets for therapeutic intervention due to their extensive roles in human physiology and the pathophysiology of disease. Many successful drugs targeting this gene family have been discovered for diseases such as hypertension, epilepsy and neuropathic pain.
This symposium, the 7th in this series, will showcase the most recent advances to aid the design of new ion channel therapeutics and promote interaction between scientists with a shared interest in the field of ion channel drug discovery.
10th SCI/RSC Kinase Symposium on Inhibitor Design
9thand 10th May 2023, SCI, London, UK
Abstract submissions are now open!
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
Abstract closing dates are 7th December, 2022 (oral) and 22nd February, 2023 (poster)
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.
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EFMC ORGANISED EVENTS
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
May 21-24, 2023
IX European Workshop in Drug Synthesis (EWDSy)
June 13-16, 2023
3rd RSC BMCS Anglo-Nordic MedChem
July 5-7, 2023
57th International Conference on Medicinal Chemistry (RICT 2023)
Postdoctor in molecular tools for oligonucleotide-protein interactions, The Institute of Neuroscience and Physiology, Gothenburg SWEDEN
POST-DOCTORAL POSITION in Biochemistry, Molecular and Cellular Biology, Institut Pasteur, Paris FRANCE
Associate Professor - Biomolecular Science, & Director, Structural Genomics, University of Toronto, Toronto CANADA
Postdoctoral researcher in Chemical Biology, University of Antwerp, Antwerp BELGIUM
Various jobs opportunities, Sygnature Discovery, UNITED KINGDOM