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Dual-Specificity Phosphatase CDC25A/B Inhibitor Identified from a Focused Library with Nonelectrophilic Core Structure.

ABSTRACT: Focused libraries of enamine derivatives with a nonacidic, nonelectrophilic core structure were screened for inhibitors of dual-specificity protein phosphatases, and an o-hydroxybenzyl derivative RE44 (10d) was identified as a selective inhibitor of CDC25A/B. This inhibitor induced cell-cycle arrest of tsFT210 cells at the G2/M phase and inhibited dephosphorylation of the CDC25B substrate CDK1. Unlike most quinone-based inhibitors, 10d does not generate reactive oxygen species.

SUBMITTER: Tsuchiya A

PROVIDER: S-EPMC3324983 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Dual-Specificity Phosphatase CDC25A/B Inhibitor Identified from a Focused Library with Nonelectrophilic Core Structure.

Tsuchiya Ayako A Hirai Go G Koyama Yusuke Y Oonuma Kana K Otani Yuko Y Osada Hiroyuki H Sodeoka Mikiko M

ACS medicinal chemistry letters 20120215 4

Focused libraries of enamine derivatives with a nonacidic, nonelectrophilic core structure were screened for inhibitors of dual-specificity protein phosphatases, and an o-hydroxybenzyl derivative RE44 (10d) was identified as a selective inhibitor of CDC25A/B. This inhibitor induced cell-cycle arrest of tsFT210 cells at the G2/M phase and inhibited dephosphorylation of the CDC25B substrate CDK1. Unlike most quinone-based inhibitors, 10d does not generate reactive oxygen species. ...[more]

PMID: 22506091

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