Small-molecule kinase-inhibitor target assessment.
The identification of the cellular targets of small-molecule protein kinase inhibitors is a significant hurdle to assessing their therapeutic potential for many diseases. Here we review several biochemical and genetics-based approaches to identifying inhibitor targets. We also describe a chemical-genomics approach to kinase-inhibitor target identification and validation that matches transcriptional signatures elicited by a drug of unknown specificity and those elicited by highly specific pharmacological inhibition of engineered candidate kinase targets.
Kung
Charles
C
Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143, USA.
Shokat
Kevan M
KM
D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013379:Substrate Specificity
D047428:Protein Kinase Inhibitors; D010770:Phosphotransferases