I've spent some time over the last couple of weeks updating and adding new content to the Drug Discovery Resources section of the website.

In particular, s drug targets become more challenging medicinal chemists are looking at alternatives to small molecule competitive inhibitors, the section on covalent inhibitors have been expanded and a new page on PROTACs has been added. PROTACs are bifunctional molecules that bind to the target protein and an E3 ligase, the simultaneous PROTAC binding of two proteins brings the target protein in close enough proximity for polyubiquitination by the E2 enzyme associated to the E3 ligase, which flags the target protein for degradation through the proteasome. This offers a powerful alternative to competitive inhibition.

The Probes & Drugs portal has been added to the chemical probes page, this is a public resource joining together focused libraries of bioactive compounds (probes, drugs, specific inhibitor sets etc.) with commercially available screening libraries.

The page describing commercial fragment screening libraries has been updated to include a couple of new additions and flagging some that seem to be unavailable, if I've missed any feel free to let me know.

The section on hERG has been updated with links to new references and details of hERGcentral.

hERGCentral: A Large Database to Store, Retrieve, and Analyze Compound-Human Ether-à-go-go Related Gene Channel Interactions to Facilitate Cardiotoxicity Assessment in Drug Development. The hERGCentral database hergcentral.org is based on experimental data obtained from a primary screen by electrophysiology against more than 300,000 structurally diverse compounds screened at 1 and 10uM.

Unfortunately the database appears to be no longer available. Whilst the supplementary information for the original publication does not contain the structures of the tested compounds it does reference the PubChem substance ID. I used these identifiers to download the structures of the >300,000 records and combined them with the experimental data provided in the Excel tables in the supplementary information. The complete dataset can be downloaded from the hERG page.

Small molecules can potentially bind to a variety of bimolecular targets and whilst counter-screening against a wide variety of targets is feasible it can be rather expensive and probably only realistic for when a compound has been identified as of particular interest. For this reason there is considerable interest in building computational models to predict potential interactions the page on predicting bioactivities has been expanded.

The section on bioisosteres also have a few new examples.

A publication by Fang et al DOI describes hERGCentral: A Large Database to Store, Retrieve, and Analyze Compound-Human Ether-à-go-go Related Gene Channel Interactions to Facilitate Cardiotoxicity Assessment in Drug Development. The hERGCentral database hergcentral.org is based on experimental data obtained from a primary screen by electrophysiology against more than 300,000 structurally diverse compounds screened at 1 and 10uM. Unfortunately the database appears to be no longer available. Whilst the supplementary information for the original publication does not contain the structures of the tested compounds it does reference the PubChem substance ID. I used these identifiers to download the structures of the >300,000 records and combined them with the experimental data provided in the Excel tables in the supplementary information. The complete dataset can be downloaded here in either

SMILES format

or in

sdf file format

Bear in mind this is single point data and there will be a fair amount of scatter.

I've added this information to the page on hERG.

I’ve updated the page on HERG activity, to include a little more information on pharmacophore models.

I’ve just updated the page on HERG activity, I’ve included the results of matched pair analysis conducted on the database of berg activity that I have been compiling.

I’ve just updated the HERG activity page. Adding new data from the literature.