Reactive compounds and in vitro false positives in HTS

An important component of the successful highthroughput screening (HTS) strategy in drug discovery is the ability to assess HTS structure-activity data, and to distinguish between promising drug leads and the many useless false positives that can plague screening efforts. The author discusses simple chemistry guidelines for the evaluation of ‘positives’ in biochemical screens, with the aim of selecting stable, non-covalent binders (ligands) and eliminating protein-reactive compounds (reagents) from consideration as drug leads at an early stage.