20S-Hydroxycholesterol
{{Chembox
| ImageFile = 20S-hydroxycholesterol.svg
| ImageSize = 200px
| IUPACName = (3S,8S,9S,10R,13S,14S,17S)-17-[(2S)-2-Hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
| OtherNames = 20α-Hydroxycholesterol; 5-Cholestene-3β,20α-diol; 20(S)-OHC
| Section1 = {{Chembox Identifiers
| CASNo = 516-72-3
| ChEBI = 166801
| ChemSpiderID = 24823271
| PubChem = 24779600
| UNII = 30060WAL99
| StdInChI=1S/C27H46O2/c1-18(2)7-6-14-27(5,29)24-11-10-22-21-9-8-19-17-20(28)12-15-25(19,3)23(21)13-16-26(22,24)4/h8,18,20-24,28-29H,6-7,9-17H2,1-5H3/t20-,21?,22?,23?,24-,25-,26-,27-/m0/s1
| StdInChIKey = MCKLJFJEQRYRQT-BEOVMOENSA-N
| SMILES = CC(C)CCC[C@@](C)([C@H]1CCC2[C@@]1(CCC3C2CC=C4[C@@]3(CC[C@@H](C4)O)C)C)O
}}
| Section2 = {{Chembox Properties
| C=27 | H=46 | O=2
| Appearance =
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| Section3 = {{Chembox Hazards
| MainHazards =
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20S-Hydroxycholesterol is a steroid of the oxysterol class. It is a human metabolite of cholesterol.
20S-Hydroxycholesterol has been the subject of research into its role in human health. For example, 20S-hydroxycholesterol has been found to be an allosteric activator of the Hedgehog signaling pathway, which has implications in cancer research.{{cite journal | doi = 10.1042/BST20180135 | title = Oxysterol research: A brief review | year = 2019 | last1 = Griffiths | first1 = William J. | last2 = Wang | first2 = Yuqin | journal = Biochemical Society Transactions | volume = 47 | issue = 2 | pages = 517–526 | pmid = 30936243 | pmc = 6490702 }}{{cite journal | pmid = 17638575 | year = 2007 | last1 = Kim | first1 = W. K. | last2 = Meliton | first2 = V. | last3 = Amantea | first3 = C. M. | last4 = Hahn | first4 = T. J. | last5 = Parhami | first5 = F. | title = 20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism | journal = Journal of Bone and Mineral Research | volume = 22 | issue = 11 | pages = 1711–1719 | doi = 10.1359/jbmr.070710 | s2cid = 935824 | doi-access = free }}{{cite journal | pmid = 22231273 | year = 2012 | last1 = Nachtergaele | first1 = S. | last2 = Mydock | first2 = L. K. | last3 = Krishnan | first3 = K. | last4 = Rammohan | first4 = J. | last5 = Schlesinger | first5 = P. H. | last6 = Covey | first6 = D. F. | last7 = Rohatgi | first7 = R. | title = Oxysterols are allosteric activators of the oncoprotein Smoothened | journal = Nature Chemical Biology | volume = 8 | issue = 2 | pages = 211–220 | doi = 10.1038/nchembio.765 | pmc = 3262054 }}{{cite journal | pmid = 17200122 | year = 2007 | last1 = Dwyer | first1 = J. R. | last2 = Sever | first2 = N. | last3 = Carlson | first3 = M. | last4 = Nelson | first4 = S. F. | last5 = Beachy | first5 = P. A. | last6 = Parhami | first6 = F. | title = Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells | journal = The Journal of Biological Chemistry | volume = 282 | issue = 12 | pages = 8959–8968 | doi = 10.1074/jbc.M611741200 | doi-access = free }}{{cite journal | pmid = 23831757 | year = 2013 | last1 = Nedelcu | first1 = D. | last2 = Liu | first2 = J. | last3 = Xu | first3 = Y. | last4 = Jao | first4 = C. | last5 = Salic | first5 = A. | title = Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling | journal = Nature Chemical Biology | volume = 9 | issue = 9 | pages = 557–564 | doi = 10.1038/nchembio.1290 | pmc = 3749252 }}
More recently, 20S-hydroxycholesterol was identified as an endogenous ligand for the sigma-2 receptor, which had previously been considered an orphan receptor since its discovery in 1990.{{cite web | url = https://www.science.org/content/blog-post/another-orphan-reunited | title = Another Orphan Reunited | author = Derek Lowe | work = In The Pipeline | publisher = Science | date = November 22, 2021 }}{{cite journal | doi = 10.1038/s41589-021-00907-2| issn=1552-4450 | title = A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes | year = 2021 | last1 = Cheng | first1 = Yu-Shiuan | last2 = Zhang | first2 = Tianyi | last3 = Ma | first3 = Xiang | last4 = Pratuangtham | first4 = Sarida | last5 = Zhang | first5 = Grace C. | last6 = Ondrus | first6 = Alexander A. | last7 = Mafi | first7 = Amirhossein | last8 = Lomenick | first8 = Brett | last9 = Jones | first9 = Jeffrey J. | last10 = Ondrus | first10 = Alison E. | journal = Nature Chemical Biology | volume = 17 | issue = 12 | pages = 1271–1280 | pmid = 34799735 | pmc = 8607797 }}