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Trends Cell Biol. 2001 Apr;11(4):167-72.

Magic bullets for protein kinases.

Author information

1
Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

A chemical-genetic method for the generation of target-specific protein kinase inhibitors has been developed recently. This strategy utilizes a functionally silent active-site mutation to sensitize a target kinase to inhibition by a small molecule that does not inhibit wild-type kinases. Tyrosine and serine/threonine kinases are equally amenable to the drug-sensitization approach, which has been used to generate selective inhibitors of mutant Src-family kinases, Abl-family kinases, cyclin-dependent kinases, mitogen-activated kinases, p21-activated kinases and Ca(2+)/calmodulin-dependent kinases. The designed inhibitors are specific for the sensitized kinase in a cellular background where the wild-type kinase has been inactivated. By these means, kinase-sensitization has been used systematically to generate and analyze conditional alleles of several yeast protein kinases in vivo.

PMID:
11306297
DOI:
10.1016/s0962-8924(01)01928-6
[Indexed for MEDLINE]

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