I’ve just added a section on compounds with extended off rates from the protein target.

For indications for which require an extended pharmacological profile a compound with a long binding half-life can have a duration of action which extends beyond the presence of drug levels in plasma needed for biological activity. In particular it may be possible to extend duration of action at the intended target whilst limiting activity at off-target proteins. Whilst this could be achieved by irreversible covalent binding there is now a growing body of evidence that many small molecules can display slow off rate kinetics

Whilst fragment-based screening has been around for a while there are still groups that are new to the area. This invaluable paper provides an insight into the pit-falls that await the unwary scientist. Absolutely essential reading

In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection methods are pushed to their limits, leading to a variety of artifacts, false positives, and false negatives that too often go unrecognized. This Digest discusses some of these problems and offers suggestions to avoid them. Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening.

Learning from our mistakes: The ‘unknown knowns’ in fragment screening DOI

Whilst there are a variety of techniques to measure the properties or diversity of fragment libraries it is interesting to look at the profiles of compounds that actually appear as hits in fragment-based screening campaigns. I’ve been compiling a database of compounds that have been reported as hits in the literature, this database now has >500 entries culled from 150 publications directed at nearly 100 different molecular targets using 18 different detection technologies and might be expected to give some insight into the type of compounds that appear as hits.

You can read more here.

I’ve just updated the list of suggested books.

Included books on bioisosteres and fragment-based screening.

The registrations are coming in for the forthcoming 17th RSC/SCI Medicinal Chemistry Symposium to be held in Cambridge UK (8-11 Sept 2013). Book early to avoid disappointment.

Full details of the scientific programme are available here together with the registration form.

I’ve just updated the page containing the profiles of commercial fragment collections.

Latest Publication

Fragment library design: the evolution of fragment-based lead discovery By Dr E. Zartler, Dr C. Swain & S. Pearce
Drug Discovery World Winter 2012/13

With the growing need to streamline the drug discovery process, screening against fragment libraries rather than drug-like molecules has become increasingly adopted as an integral part of many drug discovery programmes. However, success depends on the quality of the fragment library, and many factors dictate quality.

I’m delighted to see the announcement about the European Lead Factory, hopefully this will be a huge asset for Drug Discovery. http://www.nature.com/news/europe-bets-on-drug-discovery-1.12372

Two sites shuttered by the pharmaceutical giant Merck, one in Scotland and one in the Netherlands, will soon be humming again with the work of drug discovery. But the hum will not be business as usual. It will be the sound of a public–private consortium placing a high-stakes wager: a nearly €200-million (US$271-million) bet that it can boost a languishing pharmaceutical sector by fusing academic innovation with industrial-scale screening, using robots to test chemicals for biological activity….Any academic group or company can also propose assays to test molecules in the library for biological activity. Lead-factory scientists will run these assays free of charge and confirm any promising results, working mainly in laboratory space closed by Merck in 2011 at Oss in the Netherlands. Follow-up work will be done at the University of Dundee in Scotland. Results will be provided confidentially to the groups that proposed the assays so that they can pursue further work and publications.

The latest details of the forthcoming 17th RSC/SCI Medicinal Chemistry Symposium to be held in Cambridge UK (8-11 Sept 2013) are now available.

Full details of the scientific programme are available here together with the registration form.

STEM (Science, Technology, Engineering and Mathematics) Team East is an education charity of 27 years standing.  Their aim is to promote STEM education to students.

They provide bespoke consultation on STEM enrichment to each secondary school; teacher CPD in digital electronics and CAD; teacher and pupil STEM workshops and large scale STEM Fairs (both local and regional) with hands–on practical learning activities, career events and talks. They also manage national programmes such as the Nuffield Research Bursary Scheme and the British Science Association CREST Awards. 

My children have all benefited enormously from a chance to work in science laboratories during the summer vacation, however there is the need to provide more placements, if you, your company or institution might be interested in helping please contact:-

STEM Team East 12 Ronald Rolph Court Wadloes Road Cambridge CB5 8PX http://www.stemteameast.org.uk