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

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

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 collater...

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Veröffentlicht in:Journal of medicinal chemistry 2019-03, Vol.62 (5), p.2830-2836
Hauptverfasser: Asquith, Christopher R. M, Berger, Benedict-Tilman, Wan, Jing, Bennett, James M, Capuzzi, Stephen J, Crona, Daniel J, Drewry, David H, East, Michael P, Elkins, Jonathan M, Fedorov, Oleg, Godoi, Paulo H, Hunter, Debra M, Knapp, Stefan, Müller, Susanne, Torrice, Chad D, Wells, Carrow I, Earp, H. Shelton, Willson, Timothy M, Zuercher, William J
Format: Artikel
Sprache:eng
Schlagworte:
Cyclin G - metabolism
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Male
Molecular Probes - metabolism
Protein-Serine-Threonine Kinases - metabolism
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Zusammenfassung: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.8b01213