Author/Authors :
Wooyoung Hur، نويسنده , , Anastasia Velentza، نويسنده , , Sungjoon Kim، نويسنده , , Laura Flatauer، نويسنده , , Xinnong Jiang، نويسنده , , David Valente، نويسنده , , Daniel E. Mason، نويسنده , , Melissa Suzuki، نويسنده , , Brad Larson، نويسنده , , Jianming Zhang، نويسنده , , Anna Zagorska، نويسنده , , Michael DiDonato، نويسنده , , AdvaitNagle، نويسنده , , Markus Warmuth، نويسنده , , Steven P. Balk، نويسنده , , Eric C. Peters، نويسنده , , Nathanael S. Gray، نويسنده ,
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.
Keywords :
BMX , Reactive cysteine , irreversible inhibitors , Tec-family kinase , EFGR , Quinazoline scaffold
