sphingosine 1-phosphate   Click here for help

GtoPdb Ligand ID: 911

Abbreviated name: S1P
PDB Ligand
Compound class: Metabolite
Comment: Sphingosine 1-phosphate (S1P) is a zwitterionic lyso-phospholipid product of the sphingosine biosynthetic pathway. It is a result of the phosphorylation of sphingosine by two well characterised kinases, SPHK1 and SPHK2 (sphingosine kinase 1 and 2). SPHK1 is predominately extracellular and SPHK1 intracellular. Sphingosine itself is produced by the N-deacylation of ceramide by the enzyme ceramidase.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 4
Rotatable bonds 17
Topological polar surface area 122.82
Molecular weight 379.25
XLogP 4.79
No. Lipinski's rules broken 1
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InChI InChI=1S/C18H38NO5P/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(20)17(19)16-24-25(21,22)23/h14-15,17-18,20H,2-13,16,19H2,1H3,(H2,21,22,23)/b15-14+/t17-,18+/m0/s1
1. Ancellin N, Hla T. (1999)
Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.
J Biol Chem, 274 (27): 18997-9002. [PMID:10383399]
2. Bjursell M, Gerdin AK, Jönsson M, Surve VV, Svensson L, Huang XF, Törnell J, Bohlooly-Y M. (2006)
G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice.
Biochem Biophys Res Commun, 348 (2): 359-66. [PMID:16887097]
3. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P et al.. (2002)
The immune modulator FTY720 targets sphingosine 1-phosphate receptors.
J Biol Chem, 277 (24): 21453-7. [PMID:11967257]
4. Candelore MR, Wright MJ, Tota LM, Milligan J, Shei GJ, Bergstrom JD, Mandala SM. (2002)
Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor.
Biochem Biophys Res Commun, 297 (3): 600-6. [PMID:12270137]
5. Deng Q, Clemas JA, Chrebet G, Fischer P, Hale JJ, Li Z, Mills SG, Bergstrom J, Mandala S, Mosley R et al.. (2007)
Identification of Leu276 of the S1P1 receptor and Phe263 of the S1P3 receptor in interaction with receptor specific agonists by molecular modeling, site-directed mutagenesis, and affinity studies.
Mol Pharmacol, 71 (3): 724-35. [PMID:17170199]
6. Eggerickx D, Denef JF, Labbe O, Hayashi Y, Refetoff S, Vassart G, Parmentier M, Libert F. (1995)
Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase.
Biochem J, 309 ( Pt 3): 837-43. [PMID:7639700]
7. Ignatov A, Lintzel J, Hermans-Borgmeyer I, Kreienkamp HJ, Joost P, Thomsen S, Methner A, Schaller HC. (2003)
Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development.
J Neurosci, 23 (3): 907-14. [PMID:12574419]
8. Ignatov A, Lintzel J, Kreienkamp HJ, Schaller HC. (2003)
Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled receptor GPR6 from mouse and induces intracellular Ca2+ release by activating the sphingosine-kinase pathway.
Biochem Biophys Res Commun, 311 (2): 329-36. [PMID:14592418]
9. Im DS, Clemens J, Macdonald TL, Lynch KR. (2001)
Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): structure-activity relationship of sphingosine1-phosphate receptors.
Biochemistry, 40 (46): 14053-60. [PMID:11705398]
10. Im DS, Heise CE, Ancellin N, O'Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G et al.. (2000)
Characterization of a novel sphingosine 1-phosphate receptor, Edg-8.
J Biol Chem, 275 (19): 14281-6. [PMID:10799507]
11. Jensen T, Elster L, Nielsen SM, Poda SB, Loechel F, Volbracht C, Klewe IV, David L, Watson SP. (2014)
The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function.
Bioorg Med Chem Lett, 24 (22): 5195-8. [PMID:25442311]
12. Kon J, Sato K, Watanabe T, Tomura H, Kuwabara A, Kimura T, Tamama K, Ishizuka T, Murata N, Kanda T et al.. (1999)
Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor subtypes to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells.
J Biol Chem, 274 (34): 23940-7. [PMID:10446161]
13. Ledent C, Demeestere I, Blum D, Petermans J, Hämäläinen T, Smits G, Vassart G. (2005)
Premature ovarian aging in mice deficient for Gpr3.
Proc Natl Acad Sci USA, 102 (25): 8922-6. [PMID:15956199]
14. Lobo MK, Cui Y, Ostlund SB, Balleine BW, Yang XW. (2007)
Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6.
Nat Neurosci, 10 (11): 1395-7. [PMID:17934457]
15. Murakami M, Shiraishi A, Tabata K, Fujita N. (2008)
Identification of the orphan GPCR, P2Y(10) receptor as the sphingosine-1-phosphate and lysophosphatidic acid receptor.
Biochem Biophys Res Commun, 371 (4): 707-12. [PMID:18466763]
16. Niedernberg A, Tunaru S, Blaukat A, Ardati A, Kostenis E. (2003)
Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63.
Cell Signal, 15 (4): 435-46. [PMID:12618218]
17. Okamoto H, Takuwa N, Gonda K, Okazaki H, Chang K, Yatomi Y, Shigematsu H, Takuwa Y. (1998)
EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition.
J Biol Chem, 273 (42): 27104-10. [PMID:9765227]
18. Padmanabhan S, Myers AG, Prasad BM. (2009)
Constitutively active GPR6 is located in the intracellular compartments.
FEBS Lett, 583 (1): 107-12. [PMID:19059244]
19. Pan S, Mi Y, Pally C, Beerli C, Chen A, Guerini D, Hinterding K, Nuesslein-Hildesheim B, Tuntland T, Lefebvre S et al.. (2006)
A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model.
Chem Biol, 13 (11): 1227-34. [PMID:17114004]
20. Ruiz-Medina J, Ledent C, Valverde O. (2011)
GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception.
Neuropharmacology, 61 (1-2): 43-50. [PMID:21352831]
21. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N et al.. (2004)
Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate.
J Biol Chem, 279 (14): 13839-48. [PMID:14732717]
22. Shimano K, Maeda Y, Kataoka H, Murase M, Mochizuki S, Utsumi H, Oshita K, Sugahara K. (2019)
Amiselimod (MT-1303), a novel sphingosine 1-phosphate receptor-1 functional antagonist, inhibits progress of chronic colitis induced by transfer of CD4+CD45RBhigh T cells.
PLoS One, 14 (12): e0226154. [PMID:31805144]
23. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013)
Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors.
J Biomol Screen, 18 (5): 599-609. [PMID:23396314]
24. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horré K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, Fischer DF, Pollet D, De Strooper B, Merchiers P. (2009)
The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons.
Science, 323: 946-951. [PMID:19213921]
25. Uhlenbrock K, Gassenhuber H, Kostenis E. (2002)
Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors.
Cell Signal, 14: 941-953. [PMID:12220620]
26. Van Brocklyn JR, Gräler MH, Bernhardt G, Hobson JP, Lipp M, Spiegel S. (2000)
Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6.
Blood, 95 (8): 2624-9. [PMID:10753843]
27. Van Brocklyn JR, Tu Z, Edsall LC, Schmidt RR, Spiegel S. (1999)
Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218.
J Biol Chem, 274 (8): 4626-32. [PMID:9988698]
28. Ye C, Zhang Z, Wang Z, Hua Q, Zhang R, Xie X. (2014)
Identification of a novel small-molecule agonist for human G protein-coupled receptor 3.
J Pharmacol Exp Ther, 349 (3): 437-43. [PMID:24633425]
29. Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA. (2009)
Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay.
J Biol Chem, 284: 12328-12338. [PMID:19286662]