More screening PAIN

Another valuable contribution form the Monash group on PAINS 1 – frequent hitters in screening assays. This time aminothiazoles are in the spot light – those favourites of early parallel synthesis aficionados with the mix of alpha-bromomethylketone and substituted thiourea. The authors observed issues with this motif in fragment libraries and in conventional screening decks – not necessarily that they were really bad just that they did hit frequently and were challenging to attempt to optimise – best steer clear.

In another paper 2 where the authors were screening for HDAC inhibitors using a thiol trap fluorescence read-out several series of compounds were highlighted showing activity due to thiol trapping which had not been detected with their cheminformatics filters prior to running the assay.  Compounds tended to show non-specific thiol trapping, furthermore these same compounds were shown to have activity across a range for targets (Pubchem) and unfortunately had been reported as tools for other targets. This paper is sumamrised nicely by Erlanson 3 with additional commentary on PAINS compounds

  1. S. M. Devine et al J. Med. Chem., Article ASAP DOI: 10.1021/jm501402x Publication Date (Web): January 16, 2015 Copyright © 2015, American Chemical Society
  2. J. L. Dahlin, et al, J. Med. Chem., Article ASAP DOI: 10.1021/jm5019093 Publication Date (Web): February 21, 2015 Copyright © 2015, American Chemical Society
  3. D. A. Erlanson J. Med. Chem., Article ASAP, DOI: 10.1021/acs.jmedchem.5b00294, Publication Date (Web): February 24, 2015 Copyright © 2015, American Chemical Society