WELCOME BY EFMC PRESIDENT, RUI MOREIRA
It is a privilege to welcome you on this first 2021 issue of MedChemWatch. As we enter another challenging year, MedChemWatch will continue to connect the medicinal chemistry and chemical biology community across Europe and to provide a platform for young researchers to connect.
The EFMC and the MedChemWatch team wishes you a successful and healthy 2021. Keep tuned!
NEW EFMC VISUAL IDENTITY
The EFMC is happy to unveil its new logo and visual identity. After 50 years of existence, EFMC rejuvenates its image, as it takes a leap into the digital era and opens up a new chapter of its history.
Those who know our Federation will still recognise themselves in this more dynamic and sleeker version of our beloved logo. The major change lays in the words:
European Federation for Medicinal Chemistry and Chemical Biology
EFMC strongly believes that both disciplines are part of a scientific continuum, ranging from the development of chemical tools to interrogate cellular biology, to the discovery of innovative drug candidates and clinical imaging agents. It is only natural that EFMC’s name acknowledges that it fully represents this extended community.
We invite you all to discover our new logo and to browse our website to explore our new visual identity, learn more about the Federation, its history and its core values.
The “literature spotlight” section of the newsletter will bring you a summary of the recently published research in a concise and readable way. Papers covering a range of medicinal chemistry and chemical biology from a variety of journals will be highlighted by the EFMC’s YSN’s Communication team. This month’s contribution has been brought to you by Dr Clemens Zwergel (University of Rome, IT) and his colleague Elisabetta Di Bello (University of Rome, IT).
This tenth contribution will focus on the recently published article on the “Development of a highly selective Plasmodium falciparum proteasome inhibitor with anti-malaria activity in humanized mice” (by Zhan et al. in Angewandte Chemie).
Selective antimalarial agents are urgently needed for the millions of deaths every year often related to drug resistance development. Plasmodium falciparum proteasome (Pf20S) is a promising target for parasite-selective proteasome inhibitors acting against multiple stages of the Plasmodium life cycle. In fact, Zhan et al. recently describe noncovalent Pf20S inhibitors active in these pivotal stages but with fast clearance in vivo. To identify a compound with more drug-like properties, which can be studied in mice, the team conducted an extensive structure-activity relationship (SAR) study on a macrocyclic peptide developed by Bogyo et al., via a docking workflow using LiveDesign. The full SAR data is not yet described in this first paper; however, they designed, prepared and tested the metabolically stable compound TDI-8304, highly potent against Pf3D7, and resistant P. falciparum lab strain isolates in vitro; it demonstrates specific and time-dependent inhibition of the β5 subunit of Pf20S over human proteasomes, and the combination with DHA demonstrated synergistic killing of ART-sensitive and ART-resistant parasites. TDI-8304 showed no cytotoxicity to HepG2 cells. The authors tested the promising compound in a human-mouse model of Pf infection in which the compound exhibited good PK and reduced or cleared the parasitaemia. The authors developed and evaluated the first species-selective P. falciparum proteasome noncovalent inhibitor with marked antimalarial activity in Pf infected mice, the deadliest of the Plasmodium parasites. The compound is being further evaluated to determine its suitability as a candidate for further preclinical and potentially clinical evaluation.
Gang Lin, Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi Jing Liu, Mayako Michino, Akinori Toita, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K Tumwebaze, Maria Jose Lafuente-Monasterio, Jeremie Vendome, Maria Santos Martinez-Martinez, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J Rosenthal, Roland A Cooper, Peter T Meinke, Carl F Nathan, Laura A Kirkman
Development of a highly selective Plasmodium falciparum proteasome inhibitor with anti-malaria activity in humanized mice
Angew Chem Int Ed Engl. 2021 Jan 12
DOI: 10.1002/anie.202015845 PMID: 33433953
Development of a highly selective Plasmodium falciparum proteasome inhibitor with anti-malaria activity in humanized mice - PubMed (nih.gov)
EFMC PRIZES 2021 – DEADLINE IS APPROACHING (JANUARY 31, 2021)
The deadline to apply for one of the 2021 EFMC Prize is quickly approaching!
- EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Industry
- EFMC Prize for a Young Medicinal Chemist or Chemical Biologist in Academia
The two Prizes are given annually and consist of a diploma, 1.000€ and an invitation to give an oral communication at the XXVI EFMC "International Symposium on Medicinal Chemistry" (EFMC-ISMC 2021), scheduled to be held virtually on August 29-September 2, 2021.
More info and applications on www.efmc.info/prizes.
The prize will consist of a diploma, a 500€ grant and free registration for the XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC 2021) and EFMC Young Medicinal Chemist Symposium (EFMC-YMCS 2021) which will take place virtually on August 29-September 2 & September 9-10, 2021.
More info and applications on www.efmc.info/ysn-phd-prize.
EFMC HONORAY FELLOWS – DEADLINE IS APPROACHING (JANUARY 31, 2021)
This life-long title and associated medal aim to recognize individuals who have provided outstanding support to the EFMC and contributed in strengthening the position of medicinal chemistry, chemical biology, or related fields in Europe.
Nominations can be submitted until January 31, 2021, and should include:
- Brief curriculum of the nominee
- Statement of the documented facts supporting the nomination, summarizing scientific achievements and support of EFMC activities. (maximum two pages)
- Two seconding nomination letters
There are no age restrictions, and nominees may have an academic or industrial background. Nominees should be European residents or have spent a considerable proportion of their career in Europe. Self-nominations are not permitted.
The award ceremony will take place during the opening of the XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC 2021), scheduled to take place in Basel, Switzerland from August 29-September 2, 2021. Appointed Honorary Fellows will be invited to attend the meeting and receive their award on stage.
More information and nominations on www.efmc.info/honorary-fellows.
EFMC-ISMC 2021 AND EFMC-YMCS 2021 WILL TAKE PLACE VIRTUALLY
The EFMC, together with the International Organising Committee has decided that the XXVI EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC 2021) will be run as a fully Virtual Event, from August 29 to September 2, 2021. We are convinced that this is the right decision to allow many scientists to safely take part in this important scientific gathering.
In agreement with the organisers, the 8th edition of the EFMC Young Medicinal Chemists' Symposium (EFMC-YMCS 2021) will also be held virtually. It will take place on September 9-10, 2021, a week after its original date to allow attendees of both events the time to rest their eyes and minds.
Both events will carry their full scientific program and participants will be able to join the event via a digital platform, with content accessible during and after the symposium.
More information about the EFMC-ISMC 2021 can be found on www.efmc-ismc.org
More information about the EFMC-YMCS 2021 can be found on www.efmc-ymcs.org
GET TO KNOW VICTOR SEBASTIAN PEREZ (EXSCIENTIA, SPAIN)
In this edition, our #Iamamedicinalchemist is the winner of the 2020 EFMC-YSN PhD Prize, Dr Victor Sebastian Perez (Exscientia, Spain)
How did you get interested in Medicinal Chemistry?
In high school I was very interested in chemistry and biology and I wanted to understand how drugs worked and how could I be able to create new tools against diseases. For this reason, when I had to apply to university, I decided to study Pharmacy as my first option. The first time I got involved in academic research was in a Medicinal Chemistry research group during my first course in Pharmacy. Since then, and after being part of several research groups, I realized that my passion was drug discovery due to its interdisciplinary nature and the possibility to create new drugs and search a real benefit in patients improving their health and quality of life.
Where and when did you obtain your PhD diploma?
I obtained my international PhD on November 2019 with the highest qualification- cum laude in the Complutense University of Madrid working mainly at the Spanish National Research Council (CSIC) in Prof. Ana Martinez’s research group, under the supervision of Dr. Carmen Gil and Dr. Nuria Campillo. Moreover, as part of my PhD and in a drive to gain new techniques, I decided to undertake research stays abroad in excellent research groups at the University of Cambridge (UK) and CONICET (Argentina) under the supervision of Prof. Sir Tom L. Blundell and Prof. Ignacio Ponzoni, respectively. Both research experiences turned out to be really exciting personal and professional adventures. All this work was possible thanks to obtaining several public and private fellowships.
What was the topic of your PhD project?
The title of my PhD thesis was “Drug Discovery for Infectious Diseases: Target-Based and Ligand-Based Approaches”. During this exciting period, I applied mainly Medicinal and Computational Chemistry tools for the discovery and development of molecules against infectious agents working both on target and ligand-based programs. One of the main projects was the PDE4NPD Consortium, funded by the European Commission, that brought together efforts to tackle Neglected Parasitic Diseases (NPDs) using phosphodiesterases (PDEs) as novel strategies. It established a multidisciplinary target-centric drug discovery platform including expert research groups and SMEs.
In addition to this, I had the opportunity to participate in several projects focused on neurodegenerative diseases drug discovery. In both areas, the application of the tools led us to identify novel promising molecules that can guide the further development of future drug candidates after an optimization program. Furthermore, novel targets were successfully explored as alternative strategies to address these unmet clinical needs.
I focused on these topics because I think that the development of novel effective treatments in both therapeutic areas is one of the biggest challenges not only for Medicinal Chemistry, but also for Global Health.
Where do you work at the moment and what is your current position?
When I finished my PhD, several opportunities from both academy and industry appealed to me in the drug discovery field. I enjoyed the environment of academic research but had also become increasingly interested in the translation of research into real drugs in the market. That’s why I finally decided to join Exscientia, an innovative pharmatech company, to acquire experience and take my first steps in the drug discovery industrial environment closer to the drug candidates.
What are your current research interests?
After being involved and acquire experience during my PhD not only in Computational-Aided Drug Discovery (CADD), but also in additional key areas for drug discovery including organic chemistry, crystallography, enzymatic assays or biophysical tools, I decided that wanted to continue working mainly in the CADD field. For this reason, I am now focused in drug discovery from a computational perspective using the advances of artificial intelligence to design compounds and accelerate the lead optimization and candidate identification being in close contact with expert scientist in other key areas.
What do you like most in your job?
Drug discovery includes an incredibly long and complex adventure about getting a drug to the market. In this sense, for me it is very exciting to be part of this challenging journey and contribute to achieve the aim of delivering a drug candidate that might help patients and address a clinical need. During this process, the validation of scientific hypothesis is very rewarding by receiving positive results for the new compounds we have designed and see how the programs are evolving to the hit to lead and lead optimization stages. However, when the results are not as positive as expected, and after a minute of frustration, immediately we start formulating different strategies to improve our results and face the different challenges. All the results allow us to be always learning increasing our knowledge and expertise and be closer to achieve the key objectives in the project.
What do you consider your biggest achievement in your scientific career?
I have recently finished my PhD, thus, I think that my biggest achievements are yet to come. Outside of being selected for the EFMC-YSN PhD Prize, which is a great honor, I am very happy about the positive results we have been able to achieve and my contributions to the different projects. Specially, I felt particularly rewarded that the application of the computational models yielded hit compounds in different targets and therapeutic areas during my PhD and my recent experience in Exscientia. One of my biggest aims involves contributing to the discovery and development of a drug into the market being able to make an important impact in patients’ life.
Which scientist do you admire the most and why?
I would say it is impossible to select only one. There has been an important number of scientists during the last centuries that deserves to be mentioned because of their wonderful contributions and impactful discoveries for the humanity including Sir Isaac Newton, Louis Pasteur, Alexander Fleming or Marie Curie. I would like to remark the pioneering Spanish scientists Severo Ochoa, Santiago Ramón y Cajal and mention the Spanish women scientist Margarita Salas who sadly passed away last year and with whom I had the opportunity to be seated next to in an award ceremony in 2019. Moreover, I admire many scientists I have met during my short scientific career that really inspired me.
However, I believe science, mainly nowadays, is not only about individual brilliant minds but also about teamwork and scientific collaborations specially in multidisciplinary fields. In this sense, there are many scientists that contributes everyday importantly to the development of scientific knowledge.
Did you experience any unfair situations during your scientific career?
In academic research, and mainly in countries like mine, Spain, the lack of resources for scientists that are doing a great job making substantial discoveries is very common. It is really sad to see talented young scientists working hard in impactful projects with low salaries, precarious conditions, uncertain future and lack of institutional funding and support with an excessive bureaucracy.
What would you like to ask from other medicinal chemists?
I think that probably in science we need to revise the publishing process to make it more transparent and fairer. Another point we should consider and encourage is the publication of unsuccessful results that sometimes are as important as the positive ones.
What would you guess to be the next major breakthrough in medicinal chemistry?
Novel drugs are urgently required to solve the lack of treatments in different therapeutic areas since there are still many unmet clinical needs including infectious diseases or neurodegenerative diseases. Particularly, probably biased by my background, I believe that the emergence of resistances and the new outbreaks in infectious diseases, including the current Covid-19 pandemic, are some of the main threats for global health that we need to face. The discovery of new effective treatments for infectious diseases, including the next generation of antibiotics and antiviral drugs, is one of the biggest global challenges to overcome resistance and outbreaks.
NEWS FROM THE DIVISION OF MEDICINAL CHEMISTRY OF THE GERMAN CHEMICAL SOCIETY (GDCH)
The MedChem Division of the German Chemical Society (GDCh) announces two upcoming events:
- #MedChemCASES online seminar on 21st of January 2021, 16:00 CET (website)
- Online Frontiers in Medicinal Chemistry on March 8 -10, 2021 (website)
#MEDCHEMCASES ONLINE SEMINAR
"The design of mGlu2 NAMs for neuropsychiatric disorders and tracers for PET imaging"
21st of January 2021, 16:00 CET
The MedChem Division of the German Chemical Society (GDCh) would like to invite you to the next #MedChemCASES online seminar which will be given by Michiel Van Gool, Principal Scientist at Janssen R&D, Spain.
The online seminar is free of charge, but prior registration is needed. Please sign up here
For more information on #MedChemCASES
FRONTIERS IN MEDICINAL CHEMISTRY
Online | March 8 -10, 2021
The German Chemical Society (GDCh), the German Pharmaceutical Society (DPhG) and the Swiss Chemical Society (SCS) cordially invite you to log on to the annual meeting on ´Frontiers in Medicinal Chemistry´ March 8 -10, 2021.
The online event will focus on current developments, novel approaches and cutting-edge technologies in the field of medicinal chemistry and drug research with the following sessions: Degraders and Molecular Glues, Antiviral Agents, Young Investigators, Highlights in Medicinal Chemistry, First Disclosures & Case Studies, Covalent Binders and Fragments, Cryptic Binding Pockets and Novel Methods in Medicinal Chemistry and Case Studies. The scientific program will include lectures and poster presentations. It is the goal of the organizers to make FIMC 2021 an event of scientific excellence, attractive to both industrial and academic scientists in Medicinal Chemistry, Chemical Biology, and related fields of research.
More information available here.
NEWS FROM THE BIOLOGICAL AND MEDICINAL CHEMISTRY SECTOR (BMCS) OF THE ROYAL SOCIETY OF CHEMISTRY (RSC)
The BMCS invites you to stay in touch with them via their new website or their social media channels.
- Twitter @RSC-BMCS
- LinkedIn linkedin.com/company/rsc-bmcs
- Facebook @RSCBMCS
- Instagram @RSCBMCS
- YouTube youtube.com/channel/UCMEMVT-D4vHxNU-bQQw3Ifw
The BMCS is also happy to provide a report of its recent 14th BMCS Postgraduate Symposium and announces several upcoming events.
14th BMCS POSTGRADUATE SYMPOSIUM
The 14th BMCS biological and medicinal chemistry symposium was held virtually on Friday 11th December 2020 and attracted 80 abstracts and 240 registered attendees, two plenary lectures and eight young researcher lectures. There were also 22 poster presentations and the quality of the science presented was yet again extremely high.
The BMCS are pleased to announce that the prize awardees are as follows:
Winner: Sarah Memarzadeh (University of Glasgow)
Runner-up: Vanessa Lyne (University of Durham)
Winner: Ross Thomas (University of Strathclyde)
Runner-up: Joshua Smalley (University of Leicester)
Participant’s prize: Joseph Stephenson-Clarke (University of Southampton)
The organising committee are grateful to all those companies and individuals who provided sponsorship for this meeting, enabling the event to run free-of-charge.
Virtual - 7½th RSC / SCI symposium on GPCRs in Medicinal Chemistry
24th and 25th February 2021 (two afternoon sessions)
Synopsis: The key role of G protein-coupled receptors (GPCRs) in human disease underpins their importance to modern medicine. This series of events on GPCR drug discovery, which will combine cutting edge medicinal chemistry with innovative structural biology and novel drug design approaches.
Virtual - Synthesis in Drug Discovery and Development
22nd and 23rd March 2021 (two afternoon sessions)
Synopsis: This symposium aims to highlight and celebrate the crucial role which synthetic organic chemistry plays in the success of small molecule drug discovery. The three main themes of the symposium will be:
• Innovative synthesis facilitating candidate discovery,
• Novel bioisosteres and methodology applicable to drug discovery,
• Overcoming challenges of scale-up and process scale chemistry.
Virtual - Kinase 2021: 9th RSC / SCI symposium on kinase inhibitor design
14th and 15th April 2021 (two afternoon sessions
Synopsis: Synopsis: With more than 25 FDA-approved small molecules, the field of kinase inhibition continues to attract significant investment from the drug discovery and development community. The event will encompass case studies of ongoing programmes as well as successful past programmes.
The call for poster abstracts will close on 20th January
21st RSC / SCI Medicinal Chemistry Symposium
12th to 15th September 2021, Churchill College, Cambridge, UK
Synopsis: Europe’s premier biennial Medicinal Chemistry event, focusing on first disclosures and new strategies in medicinal chemistry.
The call for poster abstracts (first round) will close on 30th April.
THIS NEWSLETTER IS KINDLY SPONSORED BY AMERICAN ELEMENTS
ISSUE SPONSORED BY
American Elements is the world's largest manufacturer of engineered & advanced materials with a catalog of over 16,000 materials including rare earth metals, alloys, compounds and nanoparticles; high purity metals, chemicals, semiconductors and minerals; and crystal-grown materials for commercial & research applications including automotive, aerospace, military, medical, electronic, and green/clean technologies
EFMC ORGANISED EVENTS
January 28, 2021
6th EFMC-YSN MedChemBioOnline
August 29-September 2, 2021
EFMC-ISMC 2021 - XXVI EFMC International Symposium on Medicinal Chemistry
September 9-10, 2021
EFMC-YMCS 2021 - 8th EFMC Young Medicinal Chemists’ Symposium
Oegstgeest, The Netherlands
16th EFMC Short Course on Medicinal Chemistry - New Opportunities in GPCR Drug Discovery
EFMC SPONSORED EVENTS
February 25-27, 2021
18th Hellenic Symposium on Medicinal Chemistry (HSMC-18)
April 29, 2021
The 3rd SCI-RSC Symposium on Transporters in Drug Discovery and Development
Research Assistant (PhD Student)
Philipps-Universität Marburg, Marburg, Germany
Postdoctoral researcher with subsidy Medicinal Chemistry
University of Antwerp, Department of Pharmaceutical Sciences Antwerp, Belgium
PhD student Medicinal Chemistry, University of Antwerp, Department of Pharmaceutical Sciences Antwerp, Belgium
Postdoctoral Researcher in Glycochemistry, University of Basel, Molecular Pharmacy, Department of Pharmaceutical Sciences, Basel, Switzerland
PhD student in Medicinal Chemistry, Technische Universität Braunschweig, Institute of Medicinal and Pharmaceutical Chemistry, Braunschweig, Germany
Postdoctoral Researcher Medicinal Chemistry (2 Positions), University of Antwerp, Department of Pharmaceutical Sciences, Antwerp, Belgium
Drug Hunter @Aqemia, France (Paris) - deeptech startup leveraging AI and quantum-inspired physics for drug discovery, AQEMIA, Paris, France
Analytical Chemist (Job Code AC) for the quality control of our chemical compound collection EU-OPENSCREEN ERIC, Compound Team Berlin, Germany
Postdoc in Computational Chemistry, University of Hradec Kralove, Department of Chemistry Hradec Kralove, Czech Republic