Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.
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ABSTRACT:
SUBMITTER: Hur W
PROVIDER: S-EPMC2610413 | biostudies-literature | 2008 Nov
REPOSITORIES: biostudies-literature
Publications
Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.
Hur Wooyoung W Velentza Anastasia A Kim Sungjoon S Flatauer Laura L Jiang Xinnong X Valente David D Mason Daniel E DE Suzuki Melissa M Larson Brad B Zhang Jianming J Zagorska Anna A Didonato Michael M Nagle Advait A Warmuth Markus M Balk Steven P SP Peters Eric C EC Gray Nathanael S NS
Bioorganic & medicinal chemistry letters 20080718 22
Irreversible HER/erbB inhibitors selectively inhibit HER-family kinases by targeting a unique cysteine residue located within the ATP-binding pocket. Sequence alignment reveals that this rare cysteine is also present in ten other protein kinases including all five Tec-family members. We demonstrate that the Tec-family kinase Bmx is potently inhibited by irreversible modification at Cys496 by clinical stage EGFR inhibitors such as CI-1033. This cross-reactivity may have significant clinical impli ...[more]
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