Pharmacophore modelling of 17β-HSD1 enzyme based on active inhibitors and enzyme structure

Abstract The 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) enzyme regulates the conversion of estrone (E1) to the biologically active estradiol (E2). Due to its role as a key enzyme in female hormone production, it has emerged as an attractive drug target for inhibitor development in relation to hormone-dependent breast cancer. Herein, we report four pharmacophore models of 17β-HSD1 based on a crystal structure, a relaxed crystal structure, a library of 17β-HSD1 inhibitors and on a docked complex of 17βHSD1 enzyme and a potent inhibitor. The models were used in screening two databases, which produced novel compounds to be used as leads in our drug design project. The results were validated by docking the compounds to the active site of the 17β-HSD1 enzyme. With the help of our 3D-QSAR model, these results will be used to develop new inhibitors of 17β-HSD1 as drug candidates.