11α-Hydroxyprogesterone

Chemical compound 17α-hydroxyprogesterone (8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one 11α-Hydroxyprogesterone.svg skin-invert-image 225px correct CAS 80-75-1 92730 83709 correct FDA D8X4JXL4VM 16076 1563246 11α-OHP; 11α-Hydroxypregn-4-ene-3,20-dione; 4-Pregnen-11α-ol-3,20-dione; δ4-Pregnen-11α-ol-3,20-dione 21 30 3 CC(=O)C1CCC2C1(CC(C3C2CCC4=CC(=O)CCC34C)O)C 1S/C21H30O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-19,24H,4-9,11H2,1-3H3/t15-,16+,17-,18+,19+,20-,21+/m0/s1 BFZHCUBIASXHPK-QJSKAATBSA-N 11α-Hydroxyprogesterone (11α-OHP), or 11α-hydroxypregn-4-ene-3,20-dione is an endogenous steroid and metabolite of progesterone. Ford DH Effect of 11 alpha-hydroxyprogesterone on reproductive system of normal and pregnant adult wistar rats The Journal of Clinical Endocrinology and Metabolism 14 10 1268–1270 October 1954 13201630 10.1210/jcem-14-10-1268 Souness GW, Latif SA, Laurenzo JL, Morris DJ 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat Endocrinology 136 4 1809–1812 April 1995 7895695 10.1210/endo.136.4.7895695 Souness GW, Morris DJ 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat Hypertension 27 3 Pt 1 421–425 March 1996 8698448 10.1161/01.hyp.27.3.421 It is a weak antiandrogen, and is devoid of androgenic, estrogenic, and progestogenic activity. Lerner LJ Androgen antagonists Pharmacology & Therapeutics B 1 2 217–231 1975 772705 10.1016/0306-039X(75)90006-9 11α Hydroxyprogesterone, while devoid of androgenic, estrogenic and progestational activity, is weakly anti androgenic in castrate rats. Nguyen KT, Virus C, Günnewich N, Hannemann F, Bernhardt R Changing the regioselectivity of a P450 from C15 to C11 hydroxylation of progesterone ChemBioChem 13 8 1161–1166 May 2012 22532270 10.1002/cbic.201100811 11α-Hydroxyprogesterone is an important pharmaceutical compound with anti-androgenic and blood-pressure-regulating activity. [...] 11α-Hydroxyprogesterone can therefore influence blood pressure regulation.12 Furthermore, 11α-hydroxyprogesterone exhibits an anti-androgenic activity with minimal estrogenic and progestational side effects.13 This substance has been proposed for treating skin diseases, especially for psoriasis in combination with clobetasol propionate and minoxidil.14. 34483686 Tindall DJ, Chang CH, Lobl TJ, Cunningham GR Androgen antagonists in androgen target tissues Pharmacology & Therapeutics 24 3 367–400 1984 6205409 10.1016/0163-7258(84)90010-X 11α-OHP was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and was found to produce some benefit. Millikan LE Drug Therapy in Dermatology https://books.google.com/books?id=3TDMBQAAQBAJ&pg=PA403 19 April 2016 CRC Press 978-0-203-90831-0 403 Topical antiandrogens have also been tried, including topical progesterone, which proved ineffective. However, small studies with topical 11α-hydroxyprogesterone and 17α-estradiol showed some benefit [38,39]. In 1995, 11α-OHP, along with its epimer 11β-hydroxyprogesterone, was identified as a very potent competitive inhibitor of both isoforms (1 and 2) of 11β-hydroxysteroid dehydrogenase (11β-HSD). It is notably not metabolized by 11β-HSD2. 11α-OHP is a more potent inhibitor of 11β-HSD than enoxolone (glycyrrhetinic acid) or carbenoxolone in vitro (IC50 = 0.9 nM; IC50 = 5 nM in transfected cells). Morita H, Zhou M, Foecking MF, Gomez-Sanchez EP, Cozza EN, Gomez-Sanchez CE 11 beta-Hydroxysteroid dehydrogenase type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11 alpha-hydroxyprogesterone Endocrinology 137 6 2308–2314 June 1996 8641180 10.1210/endo.137.6.8641180 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM). free Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM 6 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response Endocrine Reviews 25 5 831–866 October 2004 15466942 10.1210/er.2003-0031 In intact cells 11α-hydroxyprogesterone is a more potent inhibitor of 11β-HSD1 than glycyrrhetinic acid or 11β-hydroxyprogesterone (117, 118). free Bujalska I, Shimojo M, Howie A, Stewart PM Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue Steroids 62 1 77–82 January 1997 9029719 10.1016/S0039-128X(96)00163-8 22551136 The compound has been found to be highly active in conferring mineralocorticoid sodium-retaining activity of corticosterone in vivo in rat bioassays and in increasing blood pressure, effects that it mediates by preventing the 11β-HSD-mediated inactivation of endogenous corticosteroids. 11α-OHP is used as a precursor in chemical syntheses of cortisone and hydrocortisone. Dunn PJ, Wells A, Williams MT Green Chemistry in the Pharmaceutical Industry https://books.google.com/books?id=sZP_bQifwc8C&pg=PA2 2 February 2010 John Wiley & Sons 978-3-527-62969-5 2– Lamberth C, Dinges J Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals https://books.google.com/books?id=Bc8vDAAAQBAJ&pg=PA250 17 May 2016 Wiley 978-3-527-69396-2 250– Ramawat KG, Mérillon JM Bioactive Molecules and Medicinal Plants https://books.google.com/books?id=rchJAAAAQBAJ&pg=PA5 16 October 2008 Springer Science & Business Media 978-3-540-74603-4 5– See also Steroidal antiandrogen List of steroidal antiandrogens Glycyrrhizin References 30em Category:11β-Hydroxysteroid dehydrogenase inhibitors Category:Cyclohexanols Category:Diketones Category:Pregnanes Category:Steroidal antiandrogens Category:Enones