Journal of Biomolecular Screening 2005-08-01

A liquid chromatography/mass spectrometry-based method for the selection of ATP competitive kinase inhibitors.

Sanjay S Khandekar, Bingbing Feng, Tracey Yi, Susan Chen, Nicholas Laping, Neal Bramson

Index: J. Biomol. Screen. 10(5) , 447-55, (2005)

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Abstract

The currently approved kinase inhibitors for therapeutic uses and a number of kinase inhibitors that are undergoing clinical trials are directed toward the adenosine triphosphate (ATP) binding site of protein kinases. The 5'-fluorosulfonylbenzoyl 5'-adenosine (FSBA) is an ATP-affinity reagent that covalently modifies a conserved lysine present in the nucleotide-binding site of most kinases. The authors have developed a liquid chromatography/mass spectrometry-based method to monitor binding of ATP competitive protein kinase inhibitors using FSBA as a nonselective activity-based probe for protein kinases. Their method provides a general, rapid, and reproducible means to screen and validate selective ATP competitive inhibitors of protein kinases.