Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase.
Article Details
- CitationCopy 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