1. SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK)
- Author
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David H. Drewry, Carrow I. Wells, James M. Bennett, Daniel J. Crona, Chad Torrice, Michael P. East, Christopher R. M. Asquith, Timothy M. Willson, Stephen J. Capuzzi, Oleg Fedorov, H. Shelton Earp, Jonathan M. Elkins, Susanne Müller, Benedict-Tilman Berger, William J. Zuercher, Debra Hunter, P.H.C. Godoi, Stefan Knapp, and Jing Wan
- Subjects
Male ,Negative control ,Chemical probe ,Protein Serine-Threonine Kinases ,01 natural sciences ,Article ,Cyclin G ,RIPK2 ,03 medical and health sciences ,Drug Discovery ,Humans ,030304 developmental biology ,Cyclin ,0303 health sciences ,Chemistry ,Kinase ,HEK 293 cells ,Intracellular Signaling Peptides and Proteins ,Highly selective ,In vitro ,0104 chemical sciences ,Cell biology ,010404 medicinal & biomolecular chemistry ,HEK293 Cells ,Molecular Probes ,Molecular Medicine - 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.
- Published
- 2019
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