| Structural highlights
3pdj is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 3d4n, 3d3e, 3czr, 3bzu, 3frj, 3fco, 3d5q |
| Gene: | HSD11, HSD11B1, HSD11L (HUMAN) |
| Activity: | 11-beta-hydroxysteroid dehydrogenase, with EC number 1.1.1.146 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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).
Publication Abstract from PubMed
The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.
Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11beta-HSD1 inhibitors.,Sun D, Wang Z, Caille S, DeGraffenreid M, Gonzalez-Lopez de Turiso F, Hungate R, Jaen JC, Jiang B, Julian LD, Kelly R, McMinn DL, Kaizerman J, Rew Y, Sudom A, Tu H, Ursu S, Walker N, Willcockson M, Yan X, Ye Q, Powers JP Bioorg Med Chem Lett. 2011 Jan 1;21(1):405-10. Epub 2010 Oct 31. PMID:21093258[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun D, Wang Z, Caille S, DeGraffenreid M, Gonzalez-Lopez de Turiso F, Hungate R, Jaen JC, Jiang B, Julian LD, Kelly R, McMinn DL, Kaizerman J, Rew Y, Sudom A, Tu H, Ursu S, Walker N, Willcockson M, Yan X, Ye Q, Powers JP. Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11beta-HSD1 inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):405-10. Epub 2010 Oct 31. PMID:21093258 doi:10.1016/j.bmcl.2010.10.129
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