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

Yanghwan Yun; Victor Sukbong Hong; Seungik Jeong; Hyeonseong Choo; Shin Kim; Jinho Lee

doi:10.1248/cpb.c21-00264

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

Yanghwan Yun, Victor Sukbong Hong, Seungik Jeong, Hyeonseong Choo, Shin Kim, Jinho Lee

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Keywords: rhodanine, inhibitor, leukemia, proviral integration site for Moloney murine leukemia virus (PIM) kinase, cancer

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2021 Volume 69 Issue 9 Pages 854-861

DOI https://doi.org/10.1248/cpb.c21-00264

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Abstract

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 = 14 nM) and modulated the expression of pBAD and p4EBP1 in a dose-dependent manner.

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