A Focused Library of Protein Tyrosine Phosphatase Inhibitors
A Focused Library of Protein Tyrosine Phosphatase Inhibitors
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DOI：
10.1021/jm100528p
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发表时间：
2010-09-23
影响因子：
7.3
通讯作者：
Seto, Christopher T.
中科院分区：
文献类型：
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作者：
Comeau, Anthony B.;Critton, David A.;Seto, Christopher T.
蛋白酪氨酸磷酸酶如PTP 1B和YopH是开发针对多种病理状况（包括糖尿病、肥胖症和鼠疫耶尔森氏菌感染）的治疗剂的潜在靶标。已经针对几种酪氨酸磷酸酶筛选了基于双齿α-酮酸的抑制剂的集中文库。化合物2a对YopH和PTP 1B的IC（50）值分别为43和220 nM，对PTP 1B的选择性是密切相关的磷酸酶TCPTP的30倍。
Protein tyrosine phosphatases such as PTP1B and YopH are potential targets for the development of therapeutic agents against a variety of pathological conditions including diabetes, obesity, and infection by the bacterium Yersinia pestis. A focused library of bidentate a-ketoacid-based inhibitors has been screened against several tyrosine phosphatases. Compound 2a has IC(50) values of 43 and 220 nM against YopH and PTP1B, respectively, and shows a 30-fold selectivity for PTP1B over the closely related phosphatase TCPTP.