| 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).
Publication Abstract from PubMed
A High Throughput Screening campaign allowed the identification of a novel class of ureas as 11beta-HSD1 inhibitors. Rational chemical optimization provided potent and selective inhibitors of both human and murine 11beta-HSD1 with an appropriate ADME profile and ex vivo activity in target tissues.
Pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1.,Venier O, Pascal C, Braun A, Namane C, Mougenot P, Crespin O, Pacquet F, Mougenot C, Monseau C, Onofri B, Dadji-Faihun R, Leger C, Ben-Hassine M, Van-Pham T, Ragot JL, Philippo C, Gussregen S, Engel C, Farjot G, Noah L, Maniani K, Nicolai E Bioorg Med Chem Lett. 2011 Apr 15;21(8):2244-51. doi: 10.1016/j.bmcl.2011.02.111., Epub 2011 Mar 23. PMID:21439819[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Venier O, Pascal C, Braun A, Namane C, Mougenot P, Crespin O, Pacquet F, Mougenot C, Monseau C, Onofri B, Dadji-Faihun R, Leger C, Ben-Hassine M, Van-Pham T, Ragot JL, Philippo C, Gussregen S, Engel C, Farjot G, Noah L, Maniani K, Nicolai E. Pyrrolidine-pyrazole ureas as potent and selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2244-51. doi: 10.1016/j.bmcl.2011.02.111., Epub 2011 Mar 23. PMID:21439819 doi:http://dx.doi.org/10.1016/j.bmcl.2011.02.111
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