Structural highlights
Function
[DHI1_CAVPO] Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with improved physiochemical properties using a deletion strategy. This strategy allowed for further optimization of potency leading to the discovery of the clinical candidate PF-915275.
N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275.,Siu M, Johnson TO, Wang Y, Nair SK, Taylor WD, Cripps SJ, Matthews JJ, Edwards MP, Pauly TA, Ermolieff J, Castro A, Hosea NA, LaPaglia A, Fanjul AN, Vogel JE Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. Epub 2009 May 7. PMID:19473839[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pu X, Yang K. Guinea pig 11beta-hydroxysteroid dehydrogenase type 1: primary structure and catalytic properties. Steroids. 2000 Mar;65(3):148-56. PMID:10699594
- ↑ Siu M, Johnson TO, Wang Y, Nair SK, Taylor WD, Cripps SJ, Matthews JJ, Edwards MP, Pauly TA, Ermolieff J, Castro A, Hosea NA, LaPaglia A, Fanjul AN, Vogel JE. N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. Epub 2009 May 7. PMID:19473839 doi:10.1016/j.bmcl.2009.05.011
