SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK)

J Med Chem. 2019 Mar 14;62(5):2830-2836. doi: 10.1021/acs.jmedchem.8b01213. Epub 2019 Feb 26.

Abstract

We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated kinase (GAK), together with a structurally related negative control SGC-GAK-1N (14). 11 was highly selective in an in vitro kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent RIPK2 inhibitor lacking GAK activity. Together, this chemical probe set can be used to interrogate GAK cellular biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin G / metabolism*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Molecular Probes / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Cyclin G
  • Intracellular Signaling Peptides and Proteins
  • Molecular Probes
  • GAK protein, human
  • Protein Serine-Threonine Kinases