Shp2 protein tyrosine phosphatase inhibitor activity of estramustine phosphate and its triterpenoid analogs

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• 作者：Latanya M. Scott^a ; Liwei Chen^a ; Kenyon G. Daniel^b ; Wesley H. Brooks^b ; Wayne C. Guida^b ; ^c ; ^d ; ^e ; Harshani R. Lawrence^b ; Said M. Sebti^c ; ^d ; Nicholas J. Lawrence^c ; ^d ; ^{nicholas.lawrence@moffitt.org} ; Jie Wu^a ; ^c ; ^d ; ^{jerry.wu@moffitt.org}
• 关键词：Shp2 ; Protein tyrosine phosphatase ; Estramustine phosphate ; Enoxolone ; Celastrol ; Triterpenoids
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 January 2011
• 年：2011
• 卷：21
• 期：2
• 页码：730-733
• 全文大小：651 K

文摘

Shp2 protein tyrosine phosphate (PTP) is a novel target for anticancer drug discovery. We identified estramustine phosphate as a Shp2 PTP inhibitor from the National Cancer Institute Approved Oncology Drug set. A focused structure–activity relationship study indicated that the 17-phosphate group is required for the Shp2 PTP inhibitor activity of estramustine phosphate. A search for estramustine phosphate analogs led to identification of two triterpenoids, enoxolone, and celastrol, having Shp2 PTP inhibitor activity. With the previously reported PTP1B inhibitor trodusquemine, our study reveals steroids and triterpenoids with negatively charged phosphate, carboxylate, or sulfonate groups as novel pharmacophores of selective PTP inhibitors.