Design and synthesis of bisubstrate inhibitors of type 1 17beta-hydroxysteroid dehydrogenase: overview and perspectives

  • Eur J Med Chem. 2008 Nov;43(11):2298-306. doi: 10.1016/j.ejmech.2008.01.044.
D Fournier  1 ,  D Poirier ,  M Mazumdar ,  S-X Lin
Affiliations
  • 1. Oncology and Molecular Endocrinology Research Center, CHUQ - Pavillon CHUL and Université Laval, 2705 Boulevard Laurier, Québec G1V 4G2, Canada.
PMID: 18372081 DOI: 10.1016/j.ejmech.2008.01.044
Abstract

Type 1 17beta-hydroxysteroid dehydrogenase (17beta-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 17beta-HSD1, the estradiol/adenosine hybrid EM-1745, is reviewed and strategies for future designs of inhibitors are proposed.