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Bioorg Med Chem Lett. 2008 Nov 15;18(22):5916-9. doi: 10.1016/j.bmcl.2008.07.062. Epub 2008 Jul 18.

Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.

Author information

1
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

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 implications.

PMID:
18667312
PMCID:
PMC2610413
DOI:
10.1016/j.bmcl.2008.07.062
[Indexed for MEDLINE]
Free PMC Article

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