An innovative kinome platform to accelerate small-molecule inhibitor discovery and optimization from hits to leads

Drug Discov Today. 2021 May;26(5):1115-1125. doi: 10.1016/j.drudis.2021.01.018. Epub 2021 Jan 23.

Abstract

Kinases, accounting for 20% of the human genome, have been the focus of pharmaceutical drug discovery efforts for over three decades. Despite concerns surrounding the tractability of kinases as drug targets, it is evident that kinase drug discovery offers great potential, underscored by the US Food and Drug Administration (FDA) approval of 48 small-molecule kinase inhibitors. Despite these successes, it is challenging to identify novel kinome selective inhibitors with good pharmacokinetic/pharmacodynamic (PK/PD) properties, and resistance to kinase inhibitor treatment frequently arises. A new era of kinase drug discovery predicates the need for diverse and powerful tools to discover the next generation of kinase inhibitors. Here, we outline key tenets of the Bristol Meyers Squibb (BMS) kinase platform, to enable efficient generation of highly optimized kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Approval
  • Drug Discovery / methods*
  • Drug Resistance
  • Humans
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / drug effects*
  • Protein Kinases / metabolism
  • United States
  • United States Food and Drug Administration

Substances

  • Protein Kinase Inhibitors
  • Protein Kinases