Please use this identifier to cite or link to this item:
|Title:||Dual Src and Abl inhibitors target wild type Abl and the AblT315I Imatinib-resistant mutant with different mechanism||Authors:||E., Crespan
|Keywords:||Src; Abl; Anticancer chemotherapy; Drug resistance; Enzyme kinetics; Tyrosine kinases||Issue Date:||2010||Project:||None||Journal:||BIOORGANIC & MEDICINAL CHEMISTRY||Abstract:||
The tyrosine kinase Src and its close homolog Abl, both play important roles in chronic myelogenous leukemia (CML) progression and Imatinib resistance. No clinically approved inhibitors of the drug-resistant AblT315I exist to date. Here, we present a thorough kinetic analysis of two potent dual Src-Abl inhibitors towards wild type Src and Abl, and the AblT315I mutant. Our results show that the most potent compound BO1 shows only a modest loss of potency (fourfold) towards the AblT315I mutant in vitro and was an ATP-competitive inhibitor of wild type Abl but it acted as a non-competitive inhibitor in the case of AblT315I.
|Appears in Collections:||Publications|
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.