Structural highlights
Disease
[DHI1_HUMAN] Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
Function
[DHI1_HUMAN] 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).
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
Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg).
Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.,McMinn DL, Rew Y, Sudom A, Caille S, Degraffenreid M, He X, Hungate R, Jiang B, Jaen J, Julian LD, Kaizerman J, Novak P, Sun D, Tu H, Ursu S, Walker NP, Yan X, Ye Q, Wang Z, Powers JP Bioorg Med Chem Lett. 2009 Mar 1;19(5):1446-50. Epub 2009 Jan 15. PMID:19185488[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McMinn DL, Rew Y, Sudom A, Caille S, Degraffenreid M, He X, Hungate R, Jiang B, Jaen J, Julian LD, Kaizerman J, Novak P, Sun D, Tu H, Ursu S, Walker NP, Yan X, Ye Q, Wang Z, Powers JP. Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1446-50. Epub 2009 Jan 15. PMID:19185488 doi:10.1016/j.bmcl.2009.01.026
