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

Type 1 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD1) is a key steroidogenic enzyme that catalyses the reduction of steroid estrone into the most potent endogerrous 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 17 beta-HSD1, the estradiol/adenosine hybrid EM-1745, is reviewed and strategies for future designs of inhibitors are proposed. (C) 2008 Elsevier Masson SAS. All rights reserved.