SGX70393 Inhibits Bcr-AblT315IIn Vitro and In Vivo and Completely Suppresses Resistance When Combined with Nilotinib or Dasatinib.

Overview:Bcr-AblT315Iis detected in the majority of CML patients who relapse after dasatinib- or nilotinib-based second-line Bcr-Abl kinase inhibitor therapy. SGX70393, an azapyridine-based Abl kinase inhibitor, is effective against Bcr-Abl and Bcr-AblT315Iat low nanomolar concentrations in vitro and in cell lines. Here, we comprehensively profiled SGX70393against native and mutant Bcr-Abl in vitro and in vivo. We also used a cell-based mutagenesis screen to evaluate the resistance profile of SGX70393alone and in combination with imatinib, nilotinib, or dasatinib.