Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.
Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.
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DOI：
10.1021/acsomega.7b00144
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发表时间：
2017-05-31
期刊：
影响因子：
4.1
通讯作者：
Guy RK
中科院分区：
文献类型：
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作者：
Jarusiewicz JA;Jeon JY;Connelly MC;Chen Y;Yang L;Baker SD;Guy RK
对 St. Jude 小分子集合的细胞筛选中检测到的氨基嘧啶类似物的激酶结合能力进行分析，鉴定出一系列新型 FMS 样酪氨酸激酶 3 (FLT3) 抑制剂。结构-活性关系研究导致开发出对 FLT3 驱动的 MV4-11 和 MOLM13 急性髓性白血病细胞表现出良好效力的化合物，无论其 FLT3 突变状态如何。体外药理学分析表明，化合物 5e 显示出适合进一步临床前开发的特性。
Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure–activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.