Utilizing comprehensive and mini-kinome panels to optimize the selectivity of quinoline inhibitors for cyclin G associated kinase (GAK)

Bioorg Med Chem Lett. 2019 Jul 15;29(14):1727-1731. doi: 10.1016/j.bmcl.2019.05.025. Epub 2019 May 16.

Abstract

We demonstrate an innovative approach for optimization of kinase inhibitor potency and selectivity utilising kinase mini-panels and kinome-wide panels. We present a focused case study on development of a selective inhibitor of cyclin G associated kinase (GAK) using the quin(az)oline inhibitor chemotype. These results exemplify a versatile, efficient approach to drive kinome selectivity during inhibitor development programs.

Keywords: 4-Anilinoquinazoline; 4-anilinoquinoline; Cyclin G associated kinase (GAK); Kinome selectivity; Mini-kinome panel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin G / drug effects*
  • Humans
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinolines / antagonists & inhibitors*

Substances

  • Cyclin G
  • Protein Kinase Inhibitors
  • Quinolines
  • quinoline