Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase

…, A Zagorska, M DiDonato, A Nagle, M Warmuth…

Index: Hur, Wooyoung; Velentza, Anastasia; Kim, Sungjoon; Flatauer, Laura; Jiang, Xinnong; Valente, David; Mason, Daniel E.; Suzuki, Melissa; Larson, Brad; Zhang, Jianming; Zagorska, Anna; DiDonato, Michael; Nagle, Advait; Warmuth, Markus; Balk, Steven P.; Peters, Eric C.; Gray, Nathanael S. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 22 p. 5916 - 5919

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Citation Number: 43

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 ...