Q1 · MEDICINE
Article
Author: Crona, Daniel J. ; Zuercher, William J. ; Asquith, Christopher R. M. ; Berger, Benedict-Tilman ; Knapp, Stefan ; Hunter, Debra M. ; Capuzzi, Stephen J. ; Drewry, David H. ; Wells, Carrow I. ; Torrice, Chad D. ; Earp, H. Shelton ; Bennett, James M. ; Muller, Susanne ; Wan, Jing ; Willson, Timothy M. ; Elkins, Jonathan M. ; East, Michael P. ; Godoi, Paulo H. ; Fedorov, Oleg
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.