2. Academic Validation
  3. Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase

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.
Wooyoung Hur 1,  Anastasia Velentza,  Sungjoon Kim,  Laura Flatauer,  Xinnong Jiang,  David Valente,  Daniel E Mason,  Melissa Suzuki,  Brad Larson,  Jianming Zhang,  Anna Zagorska,  Michael Didonato,  Advait Nagle,  Markus Warmuth,  Steven P Balk,  Eric C Peters,  Nathanael S Gray
Affiliations

Affiliation

  • 1 Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
PMID: 18667312 DOI: 10.1016/j.bmcl.2008.07.062
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.

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