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First Dual Inhibitors of Steroid Sulfatase (STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Designed Multiple Ligands as Novel Potential Therapeutics for Estrogen-Dependent Diseases.
Journal of Medicinal Chemistry 2017 May 12
STS and 17β-HSD1 are attractive targets for the treatment of estrogen-dependent diseases like endometriosis and breast cancer. The simultaneous inhibition of both enzymes appears more promising than blockage of either protein alone. We describe a designed multiple ligand approach resulting in highly potent dual inhibitors. The most interesting compound 9 showed nanomolar IC50 values for both proteins, membrane permeability, and no interference with estrogen receptors. It efficiently reversed E1S- and E1-induced T47D cell proliferation.
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