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

Christopher R M AsquithBenedict-Tilman BergerJing WanJames M BennettStephen J CapuzziDaniel J CronaDavid Harold DrewryMichael P EastJonathan M ElkinsOleg FedorovPaulo H GodoiDebra M HunterStefan KnappSusanne MüllerChad D TorriceCarrow I WellsH Shelton EarpTimothy M Willson William J Zuercher

Published in: Journal of medicinal chemistry (2019)

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.

Keyphrases

cell cycle
high throughput
single cell
living cells
social media
tyrosine kinase
anti inflammatory
cell death
signaling pathway