Target (In)Validation: A Critical, Sometimes Unheralded, Role of Modern Medicinal Chemistry

ACS Med Chem Lett. 2015 May 21;6(6):618-21. doi: 10.1021/acsmedchemlett.5b00183. eCollection 2015 Jun 11.


Small molecule drug discovery commonly ventures into previously unknown and unexplored target space. For such programs, an important role of medicinal chemistry is to generate molecules that enable the most reliable conclusions from a preclinical target validation/invalidation study. Multiple facets of chemistry that provide the most rigorous results for such an experiment are highlighted.

Keywords: Target validation; biomarkers; inactive controls; proof-of-concept; target invalidation.