Discovery and characterization of a novel highly potent and selective type II native and drug-resistant V299L mutant BCR-ABL inhibitor (CHMFL-ABL-039) for Chronic Myeloid Leukemia (CML).
Jiaxin Wu, Aoli Wang, Xixiang Li, Cheng Chen, Ziping Qi, Chen Hu, Wenliang Wang, Hong Wu, Tao Huang, Ming Zhao, Wenchao Wang, Zhenquan Hu, Qingwang Liu, Beilei Wang, Li Wang, Lili Li, Jian Ge, Tao Ren, Ruixiang Xia, Jing Liu Show all
Cancer Biology & Therapy | Published : 2019
BCR fused ABL kinase is the critical driving oncogene for chronic myeloid leukemia (CML) and has been extensively studied as the drug discovery target in the past decade. The successful introduction of tyrosine kinase inhibitors (TKI) such as Imatinib, Dasatinib and Bosutinib has greatly improved the CML patient survival rate. However, upon the chronic treatment, a variety of TKI resistant mutants, such as the V299L mutant which has been found in more and more patients with the high-throughput sequencing technology, are observed, although the incidence is still considered rare compared to the more prevalent gatekeeper T315I mutant. However, with the progress of the precision medicine concept..View full abstract