Recent advances in FLT3 inhibitors for acute myeloid leukemia

被引：16

作者：

Tong, Lexian ^{[1
]}

Li, Xuemei ^{[1
]}

Hu, Yongzhou ^{[1
]}

Liu, Tao ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Peoples R China

来源：

FUTURE MEDICINAL CHEMISTRY | 2020年 / 12卷 / 10期

关键词：

acute myeloid leukemia; FLT3; inhibitor; kinase selectivity; SAR-based design; TYROSINE-KINASE INHIBITOR; DEPENDENT DENDRITIC CELLS; POTENT INHIBITOR; IN-VIVO; MULTIKINASE INHIBITOR; JAK2; DISCOVERY; DESIGN; LESTAURTINIB; MUTATION;

D O I：

10.4155/fmc-2019-0365

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fms-like tyrosine kinase-3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) cases, suggesting FLT3 as an attractive target for AML treatment. Early FLT3 inhibitors enhance antileukemia efficacy by inhibiting multiple targets, and thus had stronger off-target activity, increasing their toxicity. Recently, a number of potent and selective FLT3 inhibitors have been developed, many of which are effective against multiple mutations. This review outlines the evolution of AML-targeting FLT3 inhibitors by focusing on their chemotypes, selectivity and activity over FLT3 wild-type and FLT3 mutations as well as new techniques related to FLT3. Compounds that currently enter the late clinical stage or have entered the market are also briefly reported.

引用

页码：961 / 981

页数：21

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