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一种对急性髓系白血病有效的二氨基嘧啶FLT3抑制剂的发现。

Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.

作者信息

Jarusiewicz Jamie A, Jeon Jae Yoon, Connelly Michele C, Chen Yizhe, Yang Lei, Baker Sharyn D, Guy R Kiplin

机构信息

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, United States.

Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 W. 12th Street, Columbus, Ohio 43210, United States.

出版信息

ACS Omega. 2017 May 31;2(5):1985-2009. doi: 10.1021/acsomega.7b00144. Epub 2017 May 10.

DOI:10.1021/acsomega.7b00144
PMID:28580438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5452050/
Abstract

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 shows characteristics suitable for further preclinical development.

摘要

在对圣裘德小分子化合物库进行的细胞筛选中检测到的一种氨基嘧啶类似物的激酶结合能力分析，促成了一系列新型FMS样酪氨酸激酶3（FLT3）抑制剂的鉴定。构效关系研究促使开发出了对由FLT3驱动的MV4-11和MOLM13急性髓性白血病细胞具有良好活性的化合物，无论其FLT3突变状态如何。体外药理学分析表明，该化合物具有适合进一步临床前开发的特性。

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