In vivo antiproliferative effect of NS-187, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor, on leukemic cells harbouring Abl kinase domain mutations.

Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., 14 Nishinosho Mongucgi-Cho, Minami-Ku, Kyoto 601-8550, Japan.
Leukemia Research (Impact Factor: 2.76). 12/2006; 30(11):1443-6. DOI: 10.1016/j.leukres.2006.01.006
Source: PubMed

ABSTRACT Advanced-phase chronic myeloid leukemia patients treated with imatinib often relapse due to point mutations in the Abl kinase domain. We herein examine the in vitro and in vivo effects of a Bcr-Abl/Lyn dual tyrosine kinase inhibitor, NS-187, on seven mutated Bcr-Abl proteins. NS-187 inhibited both Tyr393-phosphorylated and Tyr393-unphosphorylated Abl, resulting in significant in vitro growth inhibition of cells expressing six of seven mutated Bcr-Abl kinases, though not T315I. Furthermore, NS-187 prolonged the survival of mice injected with leukemic cells expressing all mutated Bcr-Abl tested except T315I, and its efficacy correlated well with its in vitro effects.

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