Safety screening in early drug discovery: An optimized assay panel

摘要

Background: Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules.