BAFETINIB Dual BCR/ABL and Lyn Tyrosine Kinase Inhibitor Treatment of Chronic Myeloid Leukemia

被引:1
作者
Takeuchi, M. [2 ]
Kimura, S. [1 ]
Ashihara, E. [2 ]
Maekawa, T. [2 ]
机构
[1] J Bolos Prous Sci, Barcelona 08025, Spain
[2] Kyoto Univ Hosp, Dept Transfus Med & Cell Therapy, Sakyo Ku, Kyoto 6068507, Japan
关键词
CNS-9; INNO-406; NS-187; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DOSE IMATINIB MESYLATE; IN-VIVO; ABL; RESISTANCE; INNO-406; CELLS; INTERFERON; CYTARABINE;
D O I
10.1358/dof.2009.034.04.1338544
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The treatment of chronic myeloid leukemia (CML) has changed dramatically with the emergence of the ABL tyrosine kinase inhibitor (TKI) imatinib mesilate However, primary and secondary imatinib resistance has been frequently reported, particularly in patients with advanced-stage disease To override imatinib resistance, three second-generation ABL TKIs, i.e, dasatinib, nilotinib and bosutinib, were developed Bafetinib (INNO-406, NS-187) is a dual ABL/Lyn inhibitor developed by our team at Kyoto University Hospital in collaboration with Nippon Shinyaku Bafetinib was 25-55 times more potent than imatinib in 'blocking BCR/ABL autophosphorylation, while otherwise retaining specificity for ABL and Lyn Bafetinib had antiproliferative effects 'against cells bearing wild-type or most mutated BCR/ABL proteins, except T3151, and also inhibited BCR/ABL-positive leukemic cell growth in the central nervous system A phase I sturdy on bofetinib was completed and the agent was well tolerated and demonstrated clinical activity across a range of doses Responses occurred even in the setting of a heavily pretreated population, thus making bofetinib a viable option for CML therapy.
引用
收藏
页码:261 / 269
页数:9
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