Design and synthesis of bisubstrate inhibitors of type 1 17beta-hydroxysteroid dehydrogenase: overview and perspectives.
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.
Fournier
D
D
Oncology and Molecular Endocrinology Research Center, CHUQ - Pavillon CHUL and Université Laval, 2705 Boulevard Laurier, Québec G1V 4G2, Canada.
Poirier
D
D
Mazumdar
M
M
Lin
S-X
SX
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase