Inhibitors of 11beta-HSD1: a potential treatment for the metabolic syndrome.
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11beta-HSD1 could potentially treat the metabolic syndrome. This review provides an overview of compounds reported to have in vivo inhibitory activity against this enzyme. A major focus of this review is Amgen's 11beta-HSD1 program which includes a variety of in vivo data for a lead compound from our thiazolone class of inhibitors. Finally, an update on the current known clinical data is discussed.
St Jean
David J
DJ
Department of Medicinal Chemistry, Amgen Inc., One Amgen Center Drive, Mail Stop 29-1-B, Thousand Oaks, CA 91320-1799, USA. david.st.jean@amgen.com
Wang
Minghan
M
Fotsch
Christopher
C
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy*
D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1