Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.

Article Details

Citation

Copy to clipboard

Hur W, Velentza A, Kim S, Flatauer L, Jiang X, Valente D, Mason DE, Suzuki M, Larson B, Zhang J, Zagorska A, Didonato M, Nagle A, Warmuth M, Balk SP, Peters EC, Gray NS

Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.

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

PubMed ID

18667312 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Canertinib	Epidermal growth factor receptor	IC 50 (nM)	2.3	N/A	N/A	Details