SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)

Asquith, C. R. M.; Berger, B.-T.; Wan, J.; Bennett, J. M.; East, M. P.; Elkins, J. M.; Fedorov, O.; Godoi, P. H.; Hunter, D. M.; Knapp, S.; Mueller, S.; Wells, C. I.; Earp, H. S.; Willson, T. M.; Zuercher, W. J.

doi:10.1101/376772

bioRxiv · 10.1101/376772

SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)

Asquith, C. R. M.·Berger, B.-T.·Wan, J.·Bennett, J. M.·East, M. P.·Elkins, J. M.·Fedorov, O.·Godoi, P. H.·Hunter, D. M.·Knapp, S.·Mueller, S.·Wells, C. I.·Earp, H. S.·Willson, T. M.·Zuercher, W. J.

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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). SGC-GAK-1 is highly selective in a kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent inhibitor of RIPK2 lacking GAK activity. Together, the chemical probe set of 11, 14, and 18 can be used to interrogate the cellular biology of GAK inhibition.

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Asquith, C. R. M., Berger, B.-T., Wan, J., Bennett, J. M., East, M. P., Elkins, J. M., Fedorov, O., Godoi, P. H., Hunter, D. M., Knapp, S., Mueller, S., Wells, C. I., Earp, H. S., Willson, T. M., Zuercher, W. J.. 2018-07-25. SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK). https://doi.org/10.1101/376772

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