The Hit Identification page to include information from a great analysis published recently. An Analysis of Successful Hit-to-Clinical Candidate Pairs?" DOI.

The latest Global Antibiotic Research & Development Partnership is on Project management in antimicrobial drug R&D.

Wed, Jun 7, 2023 12:30 PM - 2:00 PM BST

The webinar will feature the following speakers:

• Kristina Orrling, Programme Manager, Lygature, Netherlands
• Julie Miralves, R&D Portfolio and Planning Leader, Global Antibiotic R&D Partnership (GARDP), Switzerland

Register here https://register.gotowebinar.com/register/832555033649883487?source=network.

A couple of interesting programs to listen to.

The More or Less team are highlighting an important area. https://www.bbc.co.uk/programmes/p0fpb87t.

For more than a decade there’ve been longstanding concerns about the credibility and reliability of science research. This “bad science” has often stemmed from poor data practice or worse. But statistics can also help us identify and understand some of what’s going wrong, whether that’s selective data-slicing or outright fabrication.

There is also a more detailed investigation on Radio 4 The Truth Police https://www.bbc.co.uk/programmes/m001lqvg.

For years, science has had a dirty secret; research has been dogged by claims and instances of fraud, malpractice and outright incompetence. Suspicious-looking data sets, breakthrough results that can’t be replicated, eyebrow-raising statistical sleights of hand, science has been undergoing something of an existential crisis.

This of course has a potential profound effect on drug discovery.

A recent study, reported in Science 28 August 2015: Vol. 349 no. 6251 DOI looking at psychological science, attempted to replicate published work suggests that 39% of effects replicated the original result. Also Amgen, tried to replicate 53 'landmark' cancer studies and failed to replicate the original studies in all but six occasions, Nature 483, 531–533 (29 March 2012) DOI.

A report by Arrowsmith noted that the success rates for new development projects in Phase II trials have fallen from 28% to 18% in recent years, with insufficient efficacy being the most frequent reason for failure (Phase II failures: 2008–2010. Nature Rev. Drug Discov. 10, 328–329 (2011))1. In a follow up article Nature Reviews Drug Discovery volume 10, page 712 (2011) it was reported that that only in ∼20–25% of the projects were the relevant published data completely in line with in-house findings. This resulted in extended target validation studies and in most cases project termination.

A couple of minor updates to the Target Validation page.

https://www.cambridgemedchemconsulting.com/resources/targetvalidation.html

There have a number of headlines recently highlighting large language models (LLM https://en.wikipedia.org/wiki/Largelanguagemodel, most notably GTP-4 from OpenAI. These models are trained on vast amounts of data from a variety of sources and the quality of these data sources is not always as good as hoped.

It might be assumed the scientific literature would be of a higher standard but a recent preprint raises major concerns.

https://www.medrxiv.org/content/10.1101/2023.05.06.23289563v1

Fake Publications in Biomedical Science: Red-flagging Method Indicates Mass Production

Red-flagged fake publications (RFPs) account for around 28% of the published papers in biomedicine.

Wellcome Britain’s biggest biomedical charity is to triple the size of its genetics and biological data facilities near Cambridge, in one of the largest investments in UK research infrastructure.

https://www.wellcomegenomecampus.org/news_item/the-wellcome-genome-campus-expansion-to-boost-science-in-uk-and-health-globally/.

The site will continue to focus on genomics and biodata, aiming to attract global leaders in these fields and provide enhanced opportunities for this research to be translated into real-world solutions for health challenges. The new facilities will accommodate a range of occupiers from start-ups and scale-ups to more mature organisations, growing and enhancing the existing scientific ecosystem.

Anyone who has tried to travel down the A505 in the morning will also be interested in this item.

Upgrades to transport infrastructure, including to local road and cycle networks

Since the rail line goes right by the site could a station be included and better public transport access?

FDA Accepts Interim Analysis Plan for Ongoing Phase 2b Ibezapolstat Clinical Trial and Acurx Announces Presentations at ECCMID 2023 Scientific Conference. This is an important step for Acurx, a great group of scientists to work with.

https://ir.acurxpharma.com/press-releases/detail/52/fda-accepts-interim-analysis-plan-for-ongoing-phase-2b.

They will be presenting at the 33rd Annual European Congress of Clinical Microbiology and Infectious Disease (ECCMID) this month. Specifically, a scientific poster entitled "Novel pharmacology and susceptibility of ibezapolstat against C. difficile isolates with reduced susceptibility to C. difficile-directed antibiotics" will be presented by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy and the Principal Investigator for microbiome aspects of our ibezapolstat clinical trial program.

The Octopus trial is being led by researchers from the Queen Square MS Centre and the Medical Research Council (MRC) Clinical Trials Unit at University College London (UCL) and funded by the MS Society.

The multi-arm, multi-stage platform trial is designed to transform the way treatments for progressive MS are tested and will work up to three times faster than traditional trials.

More details…

https://www.ukri.org/news/participants-with-progressive-forms-of-ms-join-revolutionary-trial/.

More than 130,000 people live with MS in the UK and there are tens of thousands with progressive forms who have nothing to stop their MS getting worse. By tapping into the potential of approved drugs, which may have the potential to protect nerves, we can develop new treatments for MS faster.

I've always found it interesting that whilst everyone recognises that protein binding sites are three dimensional (and chiral) there is a reluctance to have chiral centres in screening hits. This is despite examples were chiral centres aid affinity, selectivity and solubility. I suspect one of the concerns is the ease of follow up for any hits.

I've been working with Liverpool Chirochem to design a 3D rich, homochiral fragment screening library. The real beauty of this library is that the fragments can be easily expanded using validated chemistry in their parallel synthesis lab.

Once you have built a supply of these homochiral building blocks they can of course be put to many different additional uses, covalent fragments, DEL building blocks, and as building blocks for large virtual libraries. All of which can be supported by their parallel synthesis lab.

Registration for the SCI / RSC 22nd Medicinal Chemistry Symposium (better known as The Cambridge MedChem Meeting) 10 September - 13 September 2023 is now open.

As usual there are discounts available for RSC and SCI members, and RSC members need to use a discount code

RSC members should enter the Event discount code EJRFChem221 and select “Guest Member” under the section Member type. Delegates will be contacted for their RSC membership number after successful registration. RSC student members should enter the Event discount code EJRFChem221S and select “Guest Member” under the section Member type. Delegates will be contacted for their RSC membership number after successful registration.

You can register here https://www.soci.org/events/fine-chemicals-group/2023/sci--rsc-22nd-medicinal-chemistry-symposium.

As usual there is an outstanding lineup of international speakers.

As part of the conference, there is also the opportunity to participate in a Medicinal Chemistry Workshop which will take place on the Sunday afternoon.