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Cambridge MedChem Consulting

Dame Carol Robinson BMCS Hall of Fame inductee

I'm really delighted to see that Dame Carol Robinson is the 2021 inductee to the RSC BMCS Hall of Fame. Her group's work on using Mass Spec to investigate biomolecular process is stunning science and her Keynote at the 2021 Cambridge MedChem meeting was one of the highlights of the meeting.

2021-Hall-of-Fame-Winner-Announcement-FINAL

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

The link between Epstein-Barr virus and multiple sclerosis has been suggested for some time but this publication in Science really underlines the importance.

"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis" DOI

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Almost everyone gets exposed to EBV (Human gammaherpesvirus 4) and it is the cause of glandular fever (aka infectious mononucleosis), after you get an EBV infection, the virus becomes latent (inactive) in your body. In some cases, the virus may reactivate. EBV infects the B cells of the immune system and epithelial cells. Once EBV's initial lytic infection is brought under control, EBV latency persists in the individual's B cells for the rest of their life.

EBV has been implicated in a variety of other diseases including various cancers.

This publication will certainly added increased interest in the Moderna the Phase I Eclipse clinical trial of its Epstein-Barr Virus (EBV) vaccine candidate, mRNA-1189. https://www.clinicaltrialsarena.com/news/moderna-ebv-vaccine-trial/.

Annual site review

As 2022 starts I'd like to wish you all a Happy New Year and hope that 2022 marks the start of the recovery from the pandemic.

The Drug Discovery Resources website continues to increase in popularity with 193,322 page views, an increase of 31% over the figure for 2020. The pages were visited by over 95,308 viewers and around 20% of the visitors come back on multiple occasions suggesting they find it useful. The visitors come from 180 different countries with the top countries being

  • United States (25%)
  • United Kingdom (14%)
  • India (13%)
  • Germany (3.6%)
  • Canada (3%)
  • South Korea (2.5%)

Perhaps not unexpectedly one of the popular pages was COVID-19 and the Identification of "Drug Candidates" a checklist for those using virtual screening to identify potential hits for COVID-19 targets.

The other most viewed pages were

Looking at the operating systems 54% are Windows users, 20% Mac users, 13% Android, 9% iOS and 2% Linux.

I don't know how comprehensive the analytics software is but there is approximately a 50:50 M:F split for Gender.

Seasons Greetings

It has been a mild winter here so far but some lovely still mornings. Take care everyone and have a great break and a successful New Year. As ever monies saved on cards will be donated to the MS Society. https://www.mssociety.org.uk.

IMG_3257

Reproducibility Project: Cancer Biology

I've been waiting for this for a while. Reproducibility Project: Cancer Biology

The Reproducibility Project: Cancer Biology was an 8-year effort to replicate experiments from high-impact cancer biology papers published between 2010 and 2012. The project was a collaboration between the Center of Open Science and Science Exchange with all papers published as part of this project available in a collection at eLife and all replication data, code, and digital materials for the project available in a collection on OSF.

The work tried to repeat 193 experiments from 53 papers and found a significant number of challenges.

ReproducibiltyReport

In summary

  • Replication effect sizes were 85% smaller on average than the original findings
  • 46% of effects replicated successfully on more criteria than they failed
  • Original positive results were half as likely to replicate successfully (40%) than original null results (80%)

This quote from In the Pipeline is perhaps a useful reminder.

A robust result can probably be reproduced even if you switch to a different buffer, or if your cell lines have been passaged a different number of times, or if the concentration of the test molecule is a bit off, etc. The more persnickity and local the conditions have to be, the less robust your result is, and in general (sad to say) the lower the odds of it having a real-world impact in drug discovery. There are certainly important things that can only be demonstrated under very precise conditions, don’t get me wrong – but when you’re expecting umpteen thousand patients to take your drug candidate and show real effects, your underlying hypothesis needs to be able to take a good kicking and still come through.

EFMC awards

To acknowledge outstanding achievements in the field of Medicinal Chemistry and Chemical Biology, EFMC confers every two years three Awards. The 2022 Awards will be presented at the XXVII EFMC "International Symposium on Medicinal Chemistry" (EFMC-ISMC 2022) to be held in Nice, France on September 4-8, 2022.

All 3 awards consist of a diploma, 7.500€ and an invitation to give a headline presentation at EFMC-ISMC 2022.

THE NAUTA PHARMACOCHEMISTRY AWARD FOR MEDICINAL CHEMISTRY AND CHEMICAL BIOLOGY

THE UCB-EHRLICH AWARD FOR EXCELLENCE IN MEDICINAL CHEMISTRY

THE PROUS INSTITUTE - OVERTON and MEYER AWARD FOR NEW TECHNOLOGIES IN DRUG DISCOVERY

More details here https://www.efmc.info/awards

Nominations for these Awards consist of a nomination letter, a brief CV including a list of selected publications and two supporting letters. Self-nominations are also accepted. The nominations should be submitted to Prof. Rui Moreira, President of the EFMC here https://www.efmc.info/custawards.php?langue=english&clemenus=1187970296

Submission deadline: January 31, 2022

2022 Summer Placements at Diamond

Applications are now open for 12-week summer placements projects available at Diamond starting in June 2022. Absolutely fantastic opportunities.

https://www.diamond.ac.uk/Careers/Students/Summer-Placement/2022-Summer-Placements1.html

Diamond Light Source is the UK’s national synchrotron. It works like a giant microscope, harnessing the power of electrons to produce bright light that scientists can use to study anything from fossils to jet engines to viruses and vaccines.

Find out more about the European Lead Factory

On Tuesday 30 November, members of the European Lead Factory (ELF) will participate in a webinar organised by the Young Scientists Network (YSN) of the European Federation of Medicinal Chemistry and Chemical Biology (EFMC).

The topic of the session is “Biological Testing of Hit Compounds”. Dr Vera Nies, Programme Manager at Lygature (the coordinating partner of the ELF) will give an introduction to the European Lead Factory. Her talk will be followed by a presentation entitled "Best practices in High Throughput Screening: ELF as an example", by Dr Steven van Helden of Pivot Park Screening Centre. The last ELF member presentation will be given by Dr Phil Jones of BioAscent, who will talk about the “Approaches Towards PAINSless Lead Generation”.

More details and registration here https://www.europeanleadfactory.eu/newsroom/elf-participate-efmc-ysn-webinar

Medicines for millions of patients

A lot has happened over the last year but one of the high spots was the latest inductee to the 2020 RSC BMCS Hall of Fame. https://www.rscbmcs.org/awards/halloffame/

The BMCS is delighted to announce that David Rees PhD, FRSC, FMedSci, Chief Scientific Officer at Astex Pharmaceuticals, will be the 2020 inductee to its Hall of Fame, and the recipient of the associated medal. David is recognised internationally for his innovative use of chemistry in drug discovery. His research has forged bridges between academia and industry and he has held prominent positions in learned societies such as the Royal Society of Chemistry. He has led collaborations resulting in the discovery of three launched drugs, the anaesthetic agent Sugammadex which has been used in over 30 million patients in 60 countries, and the anti-cancer agents Ribociclib and Erdafitinib, both predicted to achieve blockbuster status. Much of Astex’s industry-leading productivity has been dependant on David’s chemical expertise. David is well known for his calm authority, scientific rigor and enthusiasm, and has over 140 publications and patents.

David gave a fabulous presentation at the 21st RSC / SCI Medicinal Chemistry Symposium in Cambridge and I'm delighted that this talk has been converted into an article published in RSC Medicinal Chemistry.

As many of you know I'm a keen advocate of looking at the number of patients treated rather than simple sales figures and David makes this point very eloquently.


ELF programs available for partnering

The European Lead Factory (ELF) is a collaborative public-private partnership aiming to deliver innovative drug discovery starting points. The ELFgives free access to up to 550,000 novel compounds, a unique industry-standard uHTS platform, and much more.

The success of the ELF approach has been widely acknowledged and the output has shown to be of high quality, worth following up and investment-ready. Funding for further development has been secured for several programmes, and by March 2018 two programmes have led to partnering deals being closed between the Programme Owner and an established pharmaceutical company.

A number of projects are now available for partnering.

The available projects are here.

ELFprograms