SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK).
Asquith CRM., Berger B-T., Wan J., Bennett JM., Capuzzi SJ., Crona DJ., Drewry DH., East MP., Elkins JM., Fedorov O., Godoi PH., Hunter DM., Knapp S., Müller S., Torrice CD., Wells CI., Earp HS., Willson TM., Zuercher WJ.
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.