Design and synthesis of bisubstrate inhibitors of type 1 17β-hydroxysteroid dehydrogenase: Overview and perspectives

Type 1 17β-hydroxysteroid dehydrogenase (17β-HSD1) is a key steroidogenic enzyme that catalyses the reduction of steroid estrone into the most potent endogenous estrogen estradiol using the cofactor NAD(P)H. Bisubstrate inhibition is a good way to enhance the potency of inhibitors of cofactor-assisted enzymes. The design of a bisubstrate inhibitor of 17β-HSD1, the estradiol/adenosine hybrid EM-1745, is reviewed and strategies for future designs of inhibitors are proposed.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide