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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCCCCCCCCCCCCC=CC(C(COP(=O)(O)O)N)O
Isomeric SMILES CCCCCCCCCCCCC/C=C/[C@H]([C@H](COP(=O)(O)O)N)O
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
InChI Key DUYSYHSSBDVJSM-KRWOKUGFSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Natural/Endogenous Targets
Target
GPR12
GPR3
GPR63
GPR6
P2RY10
S1P1 receptor
S1P2 receptor
S1P3 receptor
S1P4 receptor
S1P5 receptor
Enzymes Catalysing Reactions with this Compound as a Substrate or Product
Enzyme EC number Reaction Reference
sphingosine-1-phosphate phosphatase 1 3.1.3.- Sphingosine 1-phosphate -> sphingosine + inorganic phosphate
dihydrosphingosine 1-phosphate -> dihydrosphingosine + inorganic phosphate
5'(3')-nucleotidase 3.1.3.- Sphingosine 1-phosphate -> sphingosine + inorganic phosphate
dihydrosphingosine 1-phosphate -> dihydrosphingosine + inorganic phosphate
Mitochondrial 5'-nucleotidase 3.1.3.- Sphingosine 1-phosphate -> sphingosine + inorganic phosphate
dihydrosphingosine 1-phosphate -> dihydrosphingosine + inorganic phosphate
sphingosine-1-phosphate phosphatase 2 3.1.3.- Sphingosine 1-phosphate -> sphingosine + inorganic phosphate
dihydrosphingosine 1-phosphate -> dihydrosphingosine + inorganic phosphate
sphingosine-1-phosphate lyase 1 4.1.2.27 Sphingosine 1-phosphate -> phosphoethanolamine + hexadecenal
dihydrosphingosine 1-phosphate -> phosphoethanolamine + hexadecanal
sphingosine kinase 1 2.7.1.91 Sphingosine + ATP = sphingosine 1-phosphate + ADP
dihydrosphingosine + ATP = dihydrosphingosine 1-phosphate + ADP
sphingosine kinase 2 2.7.1.91 Sphingosine + ATP = sphingosine 1-phosphate + ADP
dihydrosphingosine + ATP = dihydrosphingosine 1-phosphate + ADP
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
S1P5 receptor Ligand is endogenous in the given species Rn Agonist Agonist 8.7 pKd - 10
⤷ pKd 8.7 [10]
S1P1 receptor Hs Agonist Agonist 7.9 – 9.4 pKd - 5,12
⤷ pKd 7.9 – 9.4 (Kd 1.32x10-8 – 3.9x10-10 M) [5,12]
S1P3 receptor Ligand is endogenous in the given species Hs Agonist Agonist 7.6 – 9.6 pKd - 5,12,27
⤷ pKd 7.6 – 9.6 (Kd 2.62x10-8 – 2.3x10-10 M) [5,12,27]
S1P2 receptor Ligand is endogenous in the given species Hs Agonist Agonist 7.6 – 7.7 pKd - 12,27
⤷ pKd 7.6 – 7.7 (Kd 2.7x10-8 – 2.04x10-8 M) [12,27]
S1P3 receptor Ligand is endogenous in the given species Hs Agonist Agonist 8.4 – 9.8 pEC50 - 3,9,19
⤷ pEC50 8.4 – 9.8 [3,9,19]
S1P1 receptor Mm Agonist Agonist 8.9 pEC50 - 19,21
⤷ pEC50 8.9 (EC50 1.4x10-9 M) [19,21]
S1P2 receptor Ligand is endogenous in the given species Mm Agonist Agonist 8.7 pEC50 - 21
⤷ pEC50 8.7 (EC50 2x10-9 M) [21]
S1P3 receptor Ligand is endogenous in the given species Mm Agonist Agonist 8.6 pEC50 - 21
⤷ pEC50 8.6 (EC50 2.3x10-9 M) [21]
S1P1 receptor Ligand is endogenous in the given species Hs Agonist Agonist 7.1 – 9.5 pEC50 - 3,9,17,19,21-22
⤷ pEC50 9.5 (EC50 2.9x10-10 M) [22]
pEC50 7.1 – 9.4 (EC50 7.94x10-8 – 4x10-10 M) [3,9,17,19,21]
S1P2 receptor Ligand is endogenous in the given species Hs Agonist Agonist 8.1 – 8.5 pEC50 - 9,19
⤷ pEC50 8.1 – 8.5 [9,19]
S1P5 receptor Ligand is endogenous in the given species Hs Agonist Agonist 7.4 – 8.9 pEC50 - 3,9,19,21
⤷ pEC50 7.4 – 8.9 [3,9,19,21]
S1P5 receptor Ligand is endogenous in the given species Mm Agonist Agonist 7.8 – 7.9 pEC50 - 9,21
⤷ pEC50 7.8 – 7.9 (EC50 1.6x10-8 M) [9,21]
S1P4 receptor Ligand is endogenous in the given species Hs Agonist Agonist 7.2 – 8.1 pEC50 - 4,19,21
⤷ pEC50 7.2 – 8.1 (EC50 6.7x10-8 M) [4,19,21]
GPR6 Ligand is endogenous in the given species Mm Agonist Full agonist 7.3 – 7.7 pEC50 - 8,25
⤷ pEC50 7.3 – 7.7 (EC50 5.6x10-8 – 2.2x10-8 M) [8,25]
GPR3 Ligand is endogenous in the given species Hs Agonist Full agonist 7.1 – 7.7 pEC50 - 25
⤷ pEC50 7.1 – 7.7 [25]
P2RY10 Ligand is endogenous in the given species Hs Agonist Agonist 7.3 pEC50 - 15
⤷ pEC50 7.3 [15]
S1P4 receptor Ligand is endogenous in the given species Mm Agonist Agonist 7.1 pEC50 - 21
⤷ pEC50 7.1 (EC50 7.5x10-8 M) [21]
GPR12 Ligand is endogenous in the given species Hs Agonist Full agonist 5.5 – 7.0 pEC50 - 25
⤷ pEC50 5.5 – 7.0 (EC50 3.1x10-6 – 1.2x10-6 M) [25]
GPR63 Ligand is endogenous in the given species Hs Agonist Full agonist 6.1 – 6.2 pEC50 - 16
⤷ pEC50 6.1 – 6.2 (EC50 8x10-7 – 6.6x10-7 M) [16]
S1P4 receptor Ligand is endogenous in the given species Hs Agonist Agonist 6.1 – 7.0 pIC50 - 3-4
⤷ pIC50 6.1 – 7.0 [3-4]
Additional information and targets (data relate to human unless otherwise stated)
Description Data Reference
Potency order of endogenous ligands at S1P3 receptor sphingosine 1-phosphate > dihydrosphingosine 1-phosphate 17
Potency order of endogenous ligands at S1P2 receptor sphingosine 1-phosphate > dihydrosphingosine 1-phosphate 1,17
Potency order of endogenous ligands at S1P1 receptor sphingosine 1-phosphate > dihydrosphingosine 1-phosphate 1,17
Potency order of endogenous ligands at S1P4 receptor sphingosine 1-phosphate > dihydrosphingosine 1-phosphate 26
Potency order of endogenous ligands at S1P5 receptor sphingosine 1-phosphate > dihydrosphingosine 1-phosphate 10
Targets where the ligand is described in the comment field
Target Comment
GPR3 Sphingosine 1-phosphate was reported to be an endogenous agonist [25], but this finding was not replicated in subsequent studies [29]. Reported to activate adenylyl cyclase constitutively through Gs [6]. Gene disruption results in premature ovarian ageing [13], reduced β-amyloid deposition [24] and hypersensitivity to thermal pain [20] in mice. First small molecule inverse agonist [11] and agonists identified [28].
GPR63 Sphingosine 1-phosphate and dioleoylphosphatidic acid have been reported to be low affinity agonists for GPR63 [16] but this finding was not replicated in an arrestin-based assay [29].
GPR12 Reports that sphingosine 1-phosphate is a ligand of GPR12 [7,25] have not been replicated in arrestin-based assays [23,29]. Gene disruption results in dyslipidemia and obesity [2].
GPR6 An initial report that sphingosine 1-phosphate (S1P) was a high-affinity ligand (EC50 value of 39nM) [8,25] was not repeated in arrestin-based assays [23,29]. Reported to activate adenylyl cyclase constitutively through Gs and to be located intracellularly [18]. GPR6-deficient mice showed reduced striatal cyclic AMP production in vitro and selected alterations in instrumental conditioning in vivo. [14].
Ligand mentioned in the following text fields
Lysophospholipid (S1P) receptors overview
Sphingosine 1-phosphate turnover overview