Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 21, Issue 2, Pages 730-733Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.11.117
Keywords
Shp2; Protein tyrosine phosphatase; Estramustine phosphate; Enoxolone; Celastrol; Triterpenoids
Categories
Funding
- National Institutes of Health [P01CA118210, R01CA077467, P30CA076292]
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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