2-Thioxothiazolidin-4-one Analogs as Pan-PIM Kinase Inhibitors

被引：6
|
作者：
Yun, Yanghwan [1 ]
Hong, Victor Sukbong [1 ]
Jeong, Seungik [1 ]
Choo, Hyeonseong [1 ]
Kim, Shin [2 ]
Lee, Jinho [1 ]
机构：
[1] Keimyung Univ, Coll Nat Sci, Dept Chem, Daegu 42601, South Korea
[2] Keimyung Univ, Sch Med, Dept Immunol, Daegu 42601, South Korea
来源：
CHEMICAL & PHARMACEUTICAL BULLETIN | 2021年 / 69卷 / 09期
关键词：
rhodanine; inhibitor; leukemia; proviral integration site for Moloney murine leukemia virus (PIM) kinase; cancer; SELECTIVE INHIBITORS; CANCER; POTENT; DERIVATIVES; MECHANISMS; DISCOVERY; RHODANINE; SGI-1776; SCAFFOLD;
D O I：
10.1248/cpb.c21-00264
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Proviral integration site for Moloney murine leukemia virus (PIM) kinases are proto-oncogenic kinases involved in the regulation of several cellular processes. PIM kinases are promising targets for new drug development because they play a major role in many cancer-specific pathways, such as survival, apoptosis, proliferation, cell cycle regulation, and migration. Here, 2-thioxothiazolidin-4-one derivatives were synthesized and evaluated as potent pan-PIM kinase inhibitors. Optimized compounds showed single-digit nanomolar IC50 values against all three PIM kinases with high selectivity over 14 other kinases. Compound 17 inhibited the growth of Molm-16 cell lines (EC50 = 14nM) and modulated the expression of pBAD and p4EBP1 in a dose-dependent manner.
引用
收藏
页码：854 / 861
页数：8
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