MedChemWatch
Monthly Newsletter September 2022

EFMC WELCOMES A NEW NATIONAL ADHERING ORGANISATION

In our aim to showcase the Medicinal Chemistry/Chemical Biology continuum, and to represent the European scientific community at best, the EFMC is delighted to welcome the Medicinal and Biological Chemistry Division of the Institute of Chemistry of Ireland as its 30th national adhering organisation.

We warmly welcome them into our federation, and we express our sincere thanks to all those who worked together in making this fruitful collaboration possible. We look forward to working together in our common objective to advance the science of medicinal chemistry & chemical biology in Europe and around the World.

Have a look at the current list of national adhering organisations here.

LITERATURE SPOTLIGHT

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 "Target protein localization and its impact on PROTAC-mediated degradation" by  Simpson et al., 2022, Cell Chemical Biology 29, 1–23. 

Proteolysis-targeting chimeras recruit a protein of interest into spatial proximity of an E3 ubiquitin ligase, promoting POI ubiquitylation and degradation through the ubiquitin - proteasome system. Understanding how the subcellular context of the POI and the nature of the E3 ligase being recruited affects PROTAC-mediated degradation has profound implications for pairing POIs and E3 ligases for PROTAC development. Simpson et al. interrogate how the subcellular context of a target protein influences its amenability to PROTAC- mediated degradation. Differentially localized proteins displayed varying levels of degradation using the same respective PROTACs, suggesting that the subcellular context of the target protein can influence the efficacy of PROTAC-mediated POI degradation.

https://doi.org/10.1016/j.chembiol.2022.08.004

EFMC PHOTO COMPETITION 2022 – MEDCHEMBIO REALNESS

To support the EFMC efforts to showcase the reality of Medicinal Chemistry/Chemical Biology, why it is important, and what it represents in the everyday life, we sought the help of our community with a request to share a picture representing their vision of "MedChemBio Realness".

After a first round of online votes, the 10 finalists entries were displayed tothe attendees of the XXVII EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC), who then participated in selecting the winner and runners-up below!

Have a look at the results!

Photo 1

 

Grabbing most of the votes, the winner is:

  • The world we live in

PharmaChemistry D3 of the Italian Institute of Technology (Italy)

 

The two runners-up are:

  • Chromatissimo

Manuela Jörg (Monash University, Australia)

Photo 2

 

  • Smoky Reaction Souvik

Sarkar (Quretech Bio Ab, Sweden)

Photo 3

 

Congratulations to them!

Browse all submitted pictures under this link.

GET TO KNOW ANDREAS BENDER, UNIVERSITY OF CAMBRIDGE, UNITED KINGDOM

In this edition, our #Iamamedicinalchemist is Andreas Bender from the University of Cambridge, United Kingdom.

Get to know him better by reading our interview below.

Photo Andreas Bender

 

Can you describe why and where you studied chemistry, and your subsequent early career?

I always found chemistry fascinating, since my teens – micrograms of a substance can cure you, or they can kill you, it depends on the compound. That made chemistry really powerful in my mind, and I wanted to embark further into this direction, and learn more about it.

I did my diploma in Frankfurt, Germany, in 2002 in the bioinformatics area (predicting signalling peptides), and my PhD in Cambridge, UK, in the cheminformatics area in 2005, on molecular similarity. Both were excellent choices (not that I knew beforehand though, you often only know afterwards in life!), and I am still very grateful to my supervisors, Gisbert Schneider who was then in Frankfurt (I was in fact his first student there), and Bobby Glen in Cambridge, who taught me lots about ‘real-world drug discovery’. 

For my postdoc I joined Novartis in Cambridge/MA, on a Presidential Postdoctoral Fellowship – this meant the ability to work on academic research, but with all resources available in a pharmaceutical company, which was another great experience. It also shaped my thinking about the practical relevance of research today, what should be applicable in practice, to improve drug discovery. Jeremy Jenkins, Meir Glick and John Davies were my mentors there, who provided a fantastic environment to learn more, about the analysis of high-throughput screening data, as well as high-content imaging data which became very popular around my time there, in 2006/2007. I can really recommend to keep one’s mind open about academia, big pharma, start-ups (and beyond) – they all have their advantages, and you learn something different everywhere.

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

I currently have multiple roles, both at the University of Cambridge as a Professor and group leader, but in parallel I was working recently for AstraZeneca in Cambridge (in the computational safety area), Nuvisan in Berlin (setting up their Research Informatics group), and recently we started Terra Lumina, a start-up for using AI in natural product-based drug discovery. So from this it is already quite clear that my strength is also my weakness – I am interested in analysing chemical and biological data in all its breadth, in very different contexts, with respect to its ability enable theselection of compounds that are safe and efficacious in vivo.

What do you like best about your work?

What really motivates me is to use data for decision making in drug discovery – which data gives you a signal related to in vivo efficacy, and in vivo safety? So basically this means ‘putting things into practice’ – understanding which data is good for which purpose, and this is by no means clear from the onset. Often data is generated due to a ‘technology push’ (‘we can sequence, so we should’), instead of letting data generation be guided by the question. Also putting things into practice means to do the step from only aiming for a publication, towards something that is really useful in drug discovery (both of which are very different things!). I cannot claim to always have achieved it perfectly, but I try to get as close to that goal as I can.

Another aspect I find truly motivating in our area of research is its diversity, this can mean diversity from the scientific side (different data types, algorithms, and endpoints), but equally people from different countries, with very different backgrounds. I lived in multiple countries myself as well (at last count I realized I moved 23 times until that stage!), and this is what I always recommend to my students: in science it’s easy to see the world, so go to a new place on the planet, to different science, in your postdoc (or generally next stage in life).

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

There are indeed some papers that I quite like and which I am proud of – but for reasons that are maybe not so apparent from the outside. There is a story behind every paper – how the idea was developed, the people you have met and how you met them, and so on. 

The first paper I am quite proud of is from my postdoc times (https://www.nature.com/articles/nchembio.2007.53), on the integration of high-content screening data with target prediction. The reason why I quite like that is that the idea really came about during a postdoc seminar at Novartis, where both Daniel Young (the first author of the work) and myself were postdocs at the time. We met at this meeting where Daniel presented his work from the high-content screening side, I thought ‘hey, let’s add target prediction to this for the mode of action side’, and this is what led to a really nice Nature Chemical Biology publication, which combines a (then) relatively new readout type with a mechanistic angle from computational tools. 

The other publication is much more recent, while I was a PI in Cambridge, on using small molecules for the targeted differentiation of stem cells into a desired cell type, in this case cardiomyocytes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979408/). This work was done by Dr Yasaman KalantarMotamedi as a first author, and it was really fascinating that the computer, using data and algorithms, was able to select small molecules that led to a beating cardiomyocyte under the microscope – so in this way we basically generated a small part of the working heart, using the power of algorithms, chemistry, and biology. I still find this study fascinating when I think about it again.

Apart from that science is really often very incremental – you find one answer, and you have five new questions, so I am not sure this really led to me being ‘proud’ of what I did in particular. In other words, “The more you know – the more you know what you don’t know!” I think to keep the curiosity alive, like when you were young, or in your PhD, this is what keeps science going.

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

I think the most important thing in science, but maybe even as a human being, is to keep your eyes, ears, and mind open to what you currently don’t understand, to what other people say, and how other people are – which helps you develop science, but also to understand the whole world better. For example, I started out as a chemist, but during my postdoc with Novartis I was dealing with High-Content Screening Data. I first found the data very difficult to analyse (and I still do!) – but this made me realize how important it is to look at drug discovery (and associated data) across its whole range, from chemistry, to biology and pharmacology, to physiology (etc.) All of those aspects are pieces of the big puzzle of drug discovery.

An open mindset helps in science, but also more generally to learn in life. I was for example quite influenced by my trips to India: I taught in Bangalore, at the Institute for Bioinformatics and Applied Biotechnology (IBAB) for about 10 years of my life, from my postdoc years until quite recently. This only happened since I replied to an email from Karthikeyan, from NCL Pune, a bit before, but it changed my life. If you are in India you notice for example what ‘go with the flow’ means – if 10,000 people want to exit Mumbai Central Station, then you just will be unable to enter. In life of course this means to not fight situations, but to deal with them as they come, to accept how things are. 

The pictures below illustrate those years a bit – during my birthday celebration at the institute (the local tradition is to smear chocolate cake into the face of the lucky boy), as well as on the night train from Chennai to Bangalore. You get actually very good food from the vendors at the train stations, so next time you are in India, plan in a trip on the night train as well.

Photo 3

 

What is the most embarrassing thing you have done in the lab while doing experiments, e.g. explosions?

I started chemistry actually at home in my late teens – building rockets, and doing other science in what were ‘probably not entirely controlled conditions’. One time a chemical supplier sent me (to my home address!) the wrong delivery containing, among others, elementary sodium. It was too cumbersome, so apparently the supplier thought it a good idea to keep this delivery nonetheless, as a present. The label on the sodium, stored under liquid to protect from oxidation, said ‘do not bring in touch with water’, which… of course, as a teenage boy, is precisely what I did. Generation of sodium hydroxide, as well as hydrogen, and a decent explosion followed. I spent six weeks or so in hospital and nearly got blind as a result (bases cause much more serious damage to the cornea than acids), so I can confirm from empirical evidence: in case you find some elementary sodium at home, for whatever reason, do not bring into touch with water. I have realized that sometimes it is just fine to believe what one reads, and not everything needs to be proven in experiment.

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

As for resources, I can recommend for example Tom Mitchells’ ‘Machine Learning’ for an easy-to-read and very understandable introduction to the field; the blog ‘In The Pipeline’ for developments in and around the pharma area (https://www.science.org/blogs/pipeline), and TeachOpenCADD (https://volkamerlab.org/projects/teachopencadd/) from the Volkamer Lab for an hands-on introduction to the Computer-Aided Drug Discovery Field. I am also editing the Cambridge Cheminformatics Newsletter (http://www.drugdiscovery.net) with jobs and resources in the field which everyone is welcome to subscribe to, and where we organize regular events (also online) for those who are interested in the computational drug discovery field. 

What do you think about the future of your field, AI in drug discovery, and how it applies to the advancement of medicinal chemistry as a whole?

We live in really exciting times currently, be it due to new therapeutic modalities, the amount of data being generated, or the computational and algorithmic power available. From the AI in rug Discovery angle, I would like to bring some realism to the debate – do we actually have the data available so that the field can live up to its expectations? I think this will be the case in some areas more than in others – for those interested in more details, the Cambridge Crystallographic Data Centre (CCDC) put one of my recent talks online which can be found here, on the topic “Artificial Intelligence in Drug Discovery – Where Are We Today, What Do We Need to Advance Further?”, which may be of interest to the reader here: https://www.youtube.com/watch?v=PrYIChWuUFI.

EFMC SPONSORED EVENT REPORT: CHEMICAL SCIENCES IN BIOLOGICAL CHALLENGES

The three-day conference “Chemical Sciences in Biological Challenges” gathered over 120 chemistry enthusiastics from across the Europe and the USA. The conference was held in Kuopio, Finland from 15th to 17th of June.

There were 54 multidisciplinary oral presentations from topics which ranged from drug discovery and protein structure determination to micro plastics, organic synthesis, and applications of nuclear magneto-optics. Keynote lectures showcased topics such as amino phosphonates in drug design (Prof. Pawe''.chr('322').'' Kafarski), RNA dynamics studies by NMR (Assoc Prof Katja Petzold) and plastics that move, make decisions and ”learn” (Prof. Arri Priimägi).

In poster presentations, researchers presented their recent studies from which the conference participants selected the three best to be awarded with the best poster award:

  • MSc Carita Sallomy for her poster on attenuation of TRPA1  ion channel
  • MSc Iris Sokka for her poster on molecular docking of GLUT1 targeting boron carriers for BNCT
  • PhD Harri Heikkinen for his poster on ligand based NMR study of butyrylcholinesterase inhibitors.

Even though the stormy weather prevented a cruise at Lake Kallavesi, the participants enjoyed evenings with social program at the spectacular lake scenery including get-togethers with traditional Finnish food and smoke sauna as well as the conference dinner in an old wooden Casino Peräniemi.

 

Event Sponsor

Photo by Bai Krzyztof

 

Event Sponsor 2

Photo by Prof Timo Myöhänen

 

Event Sponsor 3

Photo by Univeristy of Eastern Finland

 

Event Sponsor 4

Photo by Baj Krzyztof

 

Event Sponsor 5

Photo by Prof Timo Myöhänen

EFMC CERTIFIED SCHOOL REPORT: VII SEQT SUMMER SCHOOL

The VII SEQT Summer School “Medicinal Chemistry and Chemical Biology in Drug Discovery: the Pharma Perspective”, co-organized by SEQT and Enantia, was held in Barcelona from July 19 to July 21, 2022. This meeting marked a new milestone in SEQT’s history, as the SEQT Summer School has been granted with the status of "EFMC Certified School".

More than 60 international participants attended this Summer School, with the opportunity to learn about the latest research trends in pharmaceutical drug discovery and development. The scientific program included several workshops covered by speakers from Almirall, Novartis, Janssen, Merck KGaA, FAES Farma, ENANTIA, GSK and Gate2Brain.

Since its first edition in 2009 (Janssen, Toledo), the SEQT, in collaboration with different pharma and biotech companies, has organized biannual Summer Schools that constitute a springboard for scientific discussions with the aim of introducing the pharma and biotech industry to young researchers, both graduate students and post-doctoral associates, working in the chemistry and health sciences related fields. The Summer School covered a wide variety of topics: PROTACs, ADMET properties, Bioimaging & Drug Target, Best Practices in Medicinal Chemistry, New Technologies in Organic Chemistry, Scale-up and Entrepreneurship.

Following the tradition of previous SEQT Summer Schools, in order to foster these discussions, all students were required to participate in flash presentations (two-minute/ 1-slide presentation of poster highlights) and poster sessions. Among them, the Advisory Board selected 5 students for a short oral communication presented on the final day of the school. Two awards, sponsored by ChemMedChem and ChemBioChem, were granted to the top oral communications: Isabella Ferrara (University of Zurich) and Margarida Florindo Espadinha (University of Antwerp).

The meeting was attended by 63 participants from universities, research institutions, and pharma and biotech companies belonging to 11 different countries: Spain, UK, Germany, Belgium, Romania, Italy, Portugal, Slovenia, Switzerland, Turkey and Ukraine.

The next edition of the SEQT Summer School will be hosted by Galchimia in Santiago de Compostela in 2023. Stay tuned for more information in our web site www.seqt.org

Certified School 1

Certified School 2

EFMC CERTIFIED SCHOOL REPORT: ESMEC 2022

The 41st Edition of the European School of Medicinal Chemistry (ESMEC 2022) was held in Urbino (Italy) from July 3 to July 7, 2022.

The school is organized by the Medicinal Chemistry Division of the Italian Chemical Society with the support of the European Federation for Medicinal Chemistry and Chemical Biology.

Since 2004 ESMEC has been granted with the status of "European Federation for Medicinal Chemistry accredited School"; now it is an EFMC Certified School.

The School is directed towards PhD students and young researchers from both Academia and Industry, with the aim of covering hot topics and new methodologies in medicinal chemistry.

You can find a video of ESMEC 2022 at this link: https://youtu.be/ZIIlbbPhiU8

The school was attended by 148 participants and 62 posters were presented, of which 4 were awarded.

The scientific programme included lectures on “New modalities for targeting challenging proteins”, “Electrochemistry in drug discovery”, “Rare diseases and orphan drugs” and “Market Watch: New Drug Approval in 2021 and Synthetic Strategies” and practical workshops on “Virtual reality in medicinal chemistry” and “Experiencing electrochemistry”.

A round table on “Covid and Science” with a focus on the role of medicinal chemistry also took place.

Vittorio Canale was awarded the second edition of the 'ESMEC Alumni Award'; the award is dedicated to an outstanding European researcher in the field of Medicinal Chemistry who has attended the school as a student.

Once again this year, participants created the magical atmosphere and friendship that is the other main ingredient of this school.

See you at ESMEC 2023 from July 2nd to July 6th!

Certified School ESMEC 1

Certified School ESMEC 2

Certified School ESMEC 3

Certified School ESMEC 4

#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 September 22 by Dr Nis Halland (Sanofi).

The topic of the webinar will be “Rational design and optimization of SGK1 inhibitors for the treatment osteoarthritis”

The serine/threonine kinase SGK1 is an activator of the β-catenin pathway and a powerful stimulator of cartilage degradation that is found to be upregulated under genomic control in diseased osteoarthritic cartilage. Today no oral disease-modifying treatments are available and chronic treatment in this indication sets high requirements for the drug selectivity, pharmacokinetic and safety profile. We describe the preparation of a highly selective druglike 1H-pyrazolo[3,4-d]pyrimidine SGK1 inhibitor that matches both safety and pharmacokinetic requirements for oral dosing. Rational compound design was facilitated by a novel hSGK1 cocrystal structure and classic medicinal chemistry was applied to guide the chemical optimization of ADMET and selectivity profiles.

Register for free here: https://us06web.zoom.us/webinar/register/WN_TfBsHuEqSGGpuU7SDFjhKQ

#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 BMCS Lectureship 2022/2023, and some upcoming events.

  • BMCS Lecturer for 2022/2023 is James Crawford of Genentech
  • 8th RSC/SCI symposium on GPCRs in Medicinal Chemistry
  • RSC-BMCS Targeted Protein Degradation: “Three’s a crowd?”

7th RSC-BMCS / SCI Symposium on Ion Channels as Therapeutic Targets

BMCS Lectureship for 2022/2023: Announcement

Every two years, the Biological and Medicinal Chemistry Sector (BMCS) of the RSC seeks nominations of BMCS Lecturers in response to an advertisement publicising this opportunity. The selected Lecturers are each appointed for a one-year period. We live in a time when both the process of drug discovery and the business models by which it is funded have fundamentally altered in the last generation. Yet the great benefits of new medicines to society are clear to everyone, and the expectations for future advances, as we seek to treat currently untreatable conditions, are also great

We are pleased to announce that the BMCS has made the following appointment: The BMCS Lecturer for 2022/2023 is James Crawford of Genentech. Details of the lecture venues and titles for the talks of all his lectures will be publicised on the website.

 

8th RSC/SCI symposium on GPCRs in Medicinal Chemistry

5th to 7th October 2022, Verona, Italy

Delegate Registration and Exhibitor/Sponsor registration is now open
Website:  https://www.rscbmcs.org/events/gpcrs/

Synopsis: The key role of G protein-coupled receptors (GPCRs) in human disease underpins their importance to modern medicine. We are pleased to be holding this 8th meeting in the series on GPCR drug discovery, which will combine cutting edge medicinal chemistry with innovative structural biology and novel drug design approaches

 

RSC-BMCS Targeted Protein Degradation: “Three’s a crowd ?”
16th and 17th November 2022, Virtual

Delegate Registration and Exhibitor/Sponsor registration is now open
Website: https://www.rscbmcs.org/events/protdeg22/

Synopsis: Targeted protein degradation is a rapidly developing field of drug discovery which is expanding the proportion of human proteins which are tractable drug targets. Whereas conventional small molecules are designed to block the activity of a protein, targeted protein degraders act by harnessing biological pathways to remove the protein entirely. This conference will showcase presentations showing the application and development of degradation technologies such as molecular glues and heterobifunctional degraders (e.g. PROTACs)

 

7th RSC-BMCS / SCI Symposium on Ion Channels as Therapeutic Targets
27th – 28th March 2023, Wellcome Genome Campus, Cambridge

Closing dates for oral and poster abstracts are 9th September and 31st December, respectively

Website: https://www.rscbmcs.org/ionchannels23

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 an ongoing 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.

THIS NEWSLETTER IS KINDLY SPONSORED BY


 

ISSUE SPONSORED BY

Symeres is the leading transatlantic Contract Research Organization for your drug discovery and development needs. Our services span from early stage hit finding through multiparameter medicinal chemistry, leveraging our in-house Admescope ADME-Tox platform, to the delivery of your early clinical drug substance API. We Make Molecules Matter. Together.

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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
Zagreb, Croatia
IX International Symposium on Advances in Synthetic and Medicinal Chemistry (EFMC-ASMC)

September 7-8, 2023
Zagreb, Croatia
10th EFMC Young Medicinal Chemists' Symposium (EFMC-YMCS)

November 16-18, 2023
Basel, Switzerland
EFMC International Symposium on Chemical Biology (EFMC-ISCB)

EFMC SPONSORED EVENTS

September 26-30, 2022
Heidelberg, Germany
23rd European Symposium on Quantitative Structure-Activity Relationship

September 27, 2022
Virtual Event
2nd Munich Leiden Virtual ChemBio Talks

October 5-7, 2022
Verona, Italy
8th RSC/SCI symposium on GPCRs in Medicinal Chemistry

November 23-26, 2022
Virtual Event
12th Joint Meeting on Medicinal Chemistry 2022

EFMC CERTIFIED SCHOOLS

October 9-14, 2022
Leysin, Switzerland
Swiss School on Medicinal Chemistry in Leysin

EFMC SPONSORED SCHOOLS

September 21-23, 2022
Rimini, Italy
Summer School in Pharmaceutical Analysis (SSPA2022)

JOB PORTAL

Various jobs opportunities, Sygnature Discovery UNITED KINGDOM
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Various jobs opportunities, Peak Proteins, Peak Proteins Macclesfield, UNITED KINGDOM
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Postdoctoral Research Fellow, The University of British Columbia, Vancouver, CANADA
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Post-doc in Medicinal Chemistry, University of Antwerp, Wilrijk-Antwerp, BEGLGIUM
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