The tyrosine kinase Src and its close homolog Abl, both play important roles in chronic myelogenous leukemia (CML) progression and Imatinib resistance. No clin. approved inhibitors of the drug-resistant AblT315I exist to date. Here, we present a thorough kinetic anal. of two potent dual Src-Abl inhibitors towards wild type Src and Abl, and the AblT315I mutant. Our results show that the most potent compd. BO1 (I) 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.
|Titolo:||Dual Src and Abl inhibitors target wild type Abl and the AblT315I Imatinib-resistant mutant with different mechanisms|
|Data di pubblicazione:||2010|
|Appare nelle tipologie:||01.01 - Articolo su rivista|