title: Shp2 protein tyrosine phosphatase inhibitor activity of estramustine phosphate and its triterpenoid analogs.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Latanya M
authors.initials: LM
authors.lastname: Scott
authors.forename: Liwei
authors.initials: L
authors.lastname: Chen
authors.forename: Kenyon G
authors.initials: KG
authors.lastname: Daniel
authors.forename: Wesley H
authors.initials: WH
authors.lastname: Brooks
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Guida
authors.forename: Harshani R
authors.initials: HR
authors.lastname: Lawrence
authors.forename: Said M
authors.initials: SM
authors.lastname: Sebti
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Lawrence
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry* / Q000494:pharmacology*; D004961:Estramustine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014315:Triterpenes; D004961:Estramustine; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11