2. Academic Validation
  3. SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK)

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

  • J Med Chem. 2019 Mar 14;62(5):2830-2836. doi: 10.1021/acs.jmedchem.8b01213.
Christopher R M Asquith,  Benedict-Tilman Berger 1 2,  Jing Wan,  James M Bennett 3,  Stephen J Capuzzi,  Daniel J Crona,  David H Drewry,  Michael P East,  Jonathan M Elkins 3 4,  Oleg Fedorov 3,  Paulo H Godoi 4,  Debra M Hunter,  Stefan Knapp 1 2,  Susanne Müller 1,  Chad D Torrice,  Carrow I Wells,  H Shelton Earp,  Timothy M Willson,  William J Zuercher
Affiliations

Affiliations

  • 1 Structural Genomics Consortium, Johann Wolfgang Goethe University, Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Straße 15 , D-60438 Frankfurt am Main , Germany.
  • 2 Institute for Pharmaceutical Chemistry , Johann Wolfgang Goethe University , Max-von-Laue-Straße 9 , D-60438 Frankfurt am Main , Germany.
  • 3 Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building , Oxford OX3 7DQ , U.K.
  • 4 Structural Genomics Consortium , Universidade Estadual de Campinas , Campinas , São Paulo 13083-886 , Brazil.
PMID: 30768268 DOI: 10.1021/acs.jmedchem.8b01213
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.

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