A chemoproteomic method for identifying cellular targets of covalent kinase inhibitors
Ying-Chu Chen1 and Chao Zhang1
1 Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA, USA
Correspondence:
Chao Zhang, email:
Keywords: protein kinases, covalent inhibitors, target identification
Received: April 25, 2016 Accepted: June 7, 2016 Published: June 10, 2016
Abstract
Protein kinases are attractive drug targets for numerous human diseases including cancers, diabetes and neurodegeneration. A number of kinase inhibitors that covalently target a cysteine residue in their target kinases have recently entered use in the cancer clinic. Despite the advantages of covalent kinases inhibitors, their inherent reactivity can lead to non-specific binding to other cellular proteins and cause off-target effects in cells. It is thus essential to determine the identity of these off targets in order to fully account for the phenotype and to improve the selectivity and efficacy of covalent inhibitors. Herein we present a detailed protocol for a chemoproteomic method to enrich and identify cellular targets of covalent kinase inhibitors.
