Identification of Allosteric Inhibitors of p21-Activated Kinase
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Protein kinases are among the most important drug targets; however the structural conservation of the ATP-binding pocket of kinases can lead to promiscuous inhibition of additional unintended kinase targets. Allosteric inhibitors that target less conserved regions of protein kinases represent an alternative approach that may provide more selective kinase inhibition. In this report, protocols are provided for the screening and identification of Pak1 inhibitors acting via an allosteric mechanism.
Key wordsKinase inhibitor Protein kinase Pak kinase Autoinhibition Allosteric inhibition Cdc42 Rho GTPases GTP-binding protein
This work described here was supported by a W.W. Smith Foundation Award and an American Cancer Society Scholar Award to J.R.P. and by a National Institutes of Health (NIH) award RO1 GM083025 to J.R.P.
J.V. was supported by a grant from the Fondation pour la Recherche Médicale.