20S-Hydroxycholesterol

20S-Hydroxycholesterol
Names
	IUPAC name (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
	Other names 20α-Hydroxycholesterol; 5-Cholestene-3β,20α-diol; 20(S)-OHC
Identifiers
CAS Number	516-72-3;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:166801;
ChemSpider	24823271;
PubChem CID	24779600;
UNII	30060WAL99;
	InChI InChI=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 Key: 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;
Properties
Chemical formula	C27H46O2
Molar mass	402.663 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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.^[1]^[2]^[3]^[4]^[5]

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.^[6]^[7]

References

^ Griffiths, William J.; Wang, Yuqin (2019). "Oxysterol research: A brief review". Biochemical Society Transactions. 47 (2): 517–526. doi:10.1042/BST20180135. PMC 6490702. PMID 30936243.
^ Kim, W. K.; Meliton, V.; Amantea, C. M.; Hahn, T. J.; Parhami, F. (2007). "20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism". Journal of Bone and Mineral Research. 22 (11): 1711–1719. doi:10.1359/jbmr.070710. PMID 17638575. S2CID 935824.
^ Nachtergaele, S.; Mydock, L. K.; Krishnan, K.; Rammohan, J.; Schlesinger, P. H.; Covey, D. F.; Rohatgi, R. (2012). "Oxysterols are allosteric activators of the oncoprotein Smoothened". Nature Chemical Biology. 8 (2): 211–220. doi:10.1038/nchembio.765. PMC 3262054. PMID 22231273.
^ Dwyer, J. R.; Sever, N.; Carlson, M.; Nelson, S. F.; Beachy, P. A.; Parhami, F. (2007). "Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells". The Journal of Biological Chemistry. 282 (12): 8959–8968. doi:10.1074/jbc.M611741200. PMID 17200122.
^ Nedelcu, D.; Liu, J.; Xu, Y.; Jao, C.; Salic, A. (2013). "Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling". Nature Chemical Biology. 9 (9): 557–564. doi:10.1038/nchembio.1290. PMC 3749252. PMID 23831757.
^ Derek Lowe (November 22, 2021). "Another Orphan Reunited". In The Pipeline. Science.
^ Cheng, Yu-Shiuan; Zhang, Tianyi; Ma, Xiang; Pratuangtham, Sarida; Zhang, Grace C.; Ondrus, Alexander A.; Mafi, Amirhossein; Lomenick, Brett; Jones, Jeffrey J.; Ondrus, Alison E. (2021). "A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes". Nature Chemical Biology. 17 (12): 1271–1280. doi:10.1038/s41589-021-00907-2. ISSN 1552-4450. PMC 8607797. PMID 34799735.

[1] Griffiths, William J.; Wang, Yuqin (2019). "Oxysterol research: A brief review". Biochemical Society Transactions. 47 (2): 517–526. doi:10.1042/BST20180135. PMC 6490702. PMID 30936243.

[2] Kim, W. K.; Meliton, V.; Amantea, C. M.; Hahn, T. J.; Parhami, F. (2007). "20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells through a hedgehog-dependent mechanism". Journal of Bone and Mineral Research. 22 (11): 1711–1719. doi:10.1359/jbmr.070710. PMID 17638575. S2CID 935824.

[3] Nachtergaele, S.; Mydock, L. K.; Krishnan, K.; Rammohan, J.; Schlesinger, P. H.; Covey, D. F.; Rohatgi, R. (2012). "Oxysterols are allosteric activators of the oncoprotein Smoothened". Nature Chemical Biology. 8 (2): 211–220. doi:10.1038/nchembio.765. PMC 3262054. PMID 22231273.

[4] Dwyer, J. R.; Sever, N.; Carlson, M.; Nelson, S. F.; Beachy, P. A.; Parhami, F. (2007). "Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells". The Journal of Biological Chemistry. 282 (12): 8959–8968. doi:10.1074/jbc.M611741200. PMID 17200122.

[5] Nedelcu, D.; Liu, J.; Xu, Y.; Jao, C.; Salic, A. (2013). "Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling". Nature Chemical Biology. 9 (9): 557–564. doi:10.1038/nchembio.1290. PMC 3749252. PMID 23831757.

[6] Derek Lowe (November 22, 2021). "Another Orphan Reunited". In The Pipeline. Science.

[7] Cheng, Yu-Shiuan; Zhang, Tianyi; Ma, Xiang; Pratuangtham, Sarida; Zhang, Grace C.; Ondrus, Alexander A.; Mafi, Amirhossein; Lomenick, Brett; Jones, Jeffrey J.; Ondrus, Alison E. (2021). "A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes". Nature Chemical Biology. 17 (12): 1271–1280. doi:10.1038/s41589-021-00907-2. ISSN 1552-4450. PMC 8607797. PMID 34799735.

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