Dual-specificity phosphatase CDC25A/B inhibitor identified from a focused library with nonelectrophilic core structure

Ayako Tsuchiya; Go Hirai; Yusuke Koyama; Kana Oonuma; Yuko Otani; Hiroyuki Osada; Mikiko Sodeoka

doi:10.1021/ml2002778

Dual-specificity phosphatase CDC25A/B inhibitor identified from a focused library with nonelectrophilic core structure

Ayako Tsuchiya, Go Hirai, Yusuke Koyama, Kana Oonuma, Yuko Otani, Hiroyuki Osada, Mikiko Sodeoka

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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.

Original language	English
Pages (from-to)	294-298
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	4
DOIs	https://doi.org/10.1021/ml2002778
Publication status	Published - Apr 12 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1021/ml2002778

Cite this

@article{cddcc0920a334283839fdcb55fdb2139,

title = "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.",

author = "Ayako Tsuchiya and Go Hirai and Yusuke Koyama and Kana Oonuma and Yuko Otani and Hiroyuki Osada and Mikiko Sodeoka",

year = "2012",

month = apr,

day = "12",

doi = "10.1021/ml2002778",

language = "English",

volume = "3",

pages = "294--298",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "4",

}

TY - JOUR

T1 - Dual-specificity phosphatase CDC25A/B inhibitor identified from a focused library with nonelectrophilic core structure

AU - Tsuchiya, Ayako

AU - Hirai, Go

AU - Koyama, Yusuke

AU - Oonuma, Kana

AU - Otani, Yuko

AU - Osada, Hiroyuki

AU - Sodeoka, Mikiko

PY - 2012/4/12

Y1 - 2012/4/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84859767484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859767484&partnerID=8YFLogxK

U2 - 10.1021/ml2002778

DO - 10.1021/ml2002778

M3 - Article

AN - SCOPUS:84859767484

SN - 1948-5875

VL - 3

SP - 294

EP - 298

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 4

ER -

Dual-specificity phosphatase CDC25A/B inhibitor identified from a focused library with nonelectrophilic core structure

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this