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Cambridge MedChem Consulting

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



Fluoxamine COVID-19 treatment

There have been several recent studies suggesting fluvoxamine may be beneficial when treating COVID-19 patients. Most of these reports are small trials that lack the statistical power to provide a solid answer. This has changed with the TOGETHER trial consortium who have been evaluating several different potential treatments shown in the table below. They also undertook a study investigating treatment with Ivermectin that was "stopped for futility".

togethertrials

The results of the Fluvoxamine trial have now been published "Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial" DOI. This appears to be a large (741 patients were allocated to fluvoxamine and 756 to placebo) well conducted blinded trial. The average age of the patients was 50 years, 42% male 58% female. Primary end points were related to hospitalisation. They enrolled only participants with diagnosed COVID-19 and less than 7 days of symptom onset using a commercially available COVID-19 rapid antigen test.

The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a teritary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756).

The mechanism of action is uncertain but the initial hypothesis was based on the anti-inflammatory action of fluvoxamine. Fluvoxamine is a Selective serotonin reuptake inhibitor (SSRI), however if does have other activities CHEMBL1409/

fluoxamine

SMILES = COCCCC/C(=N\OCCN)c1ccc(C(F)(F)F)cc1.O=C(O)/C=C\C(=O)O

It is worth noting Fluvoxamine is not an antiviral but it may act via anti-inflammatory effects that likely stem from its regulation of S1R, which modulates innate and adaptive immune responses and Fluvoxamine may serve to dampen cytokine storms. There have been reviews of the potential mechanism of action DOI.

Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19

Merck have just announced that the Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study.

Link to report https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/

Great news, but bear in mind this is only an interim study, so keep those fingers crossed.

Molnupiravir (development codes MK-4482 and EIDD-2801) is an experimental antiviral drug which is orally active and was developed for the treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, and exerts its antiviral action through introduction of copying errors during viral RNA replication.
MK-4482

SMILES CC(C)C(=O)OC[C@@H]1C@HN2C=CC(=NC2=O)NO)O)O
InChI=1S/C13H19N3O7/c1-6(2)12(19)22-5-7-9(17)10(18)11(23-7)16-4-3-8(15-21)14-13(16)20/h3-4,6-7,9-11,17-18,21H,5H2,1-2H3,(H,14,15,20)/t7-,9-,10-,11-/m1/s1
CHEBI https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:180653

COVID moonshot to get £8M funding

A great start to the week.

The COVID Moonshot, a non-profit, open-science consortium of scientists from around the world dedicated to the discovery of globally affordable and easily-manufactured antiviral drugs against COVID-19 and future viral pandemics has received key funding of £8 million from Wellcome, on behalf of the Covid-19 Therapeutics Accelerator.

https://dndi.org/press-releases/2021/covid-moonshot-funded-by-wellcome-to-rapidly-develop-safe-globally-accessible-affordable-antiviral-pill/.

2022 RSC Medicinal Chemistry Emerging Investigator Lectureship

Nominations are now open for the 2022 RSC Medicinal Chemistry Emerging Investigator Lectureship and close on 08 October 2021. The lectureship is open to candidates who received their PhD in 2012 or later and who have made a significant contribution to medicinal chemistry in their early career.

The RSC welcome nominations from anyone, to be sent to our journal inbox at medchem-rsc@rsc.org, but ask that nominations include the name and affiliation of the researcher, along with at least one paragraph explaining their achievements and why they should be considered (a CV is not required, but is helpful if sent along with the nomination). Additionally, self-nominations are welcomed if accompanied by a letter of support from the nominees’ institute.

There are more details about nominations on our webpage here: https://www.rsc.org/journals-books-databases/about-journals/rsc-medicinal-chemistry/#Lectureship_MChemCom.

lectureship

CYPlebrity: Machine learning models for the prediction of inhibitors of cytochrome P450 enzymes

CYPlebrity: Machine learning models for the prediction of inhibitors of cytochrome P450 enzymes DOI, https://nerdd.univie.ac.at/cyplebrity/, structures can be submitted in SMILES format or drawn using the sketcher. The calculation takes a few second per compound and the results are displayed as shown below.

cyplebrity

Added to the section on CYP Interactions.

Alphafold in Opentargets

Thanks to fantastic work from the folks at UniProt, the Open Targets Platform target profile pages now feature DeepMind’s AlphaFold data.

OpenTargetsAlphafold1

Can be easily linked to disease associations.

OpenTargetsAlphafold2