Target Information
Target General Infomation | |||||
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Target ID |
T13852
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Former ID |
TTDC00258
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Target Name |
Sphingosine 1-phosphate receptor 1
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Gene Name |
S1PR1
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Synonyms |
Endothelial differentiation G-protein coupled receptor 1; S1P receptor 1; S1P receptor Edg-1; S1P1; Sphingosine 1-phosphate receptor Edg-1; S1PR1
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Target Type |
Successful
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Disease | Advanced non-small cell lung cancer [ICD9: 162; ICD10: C33-C34] | ||||
Autoimmune diabetes [ICD10: E08-E13] | |||||
Acne vulgaris [ICD9: 706.1; ICD10: L70.0] | |||||
Cardiovascular disorder [ICD10: I00-I99] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Cutaneous lupus erythematosus [ICD9: 710; ICD10: M32] | |||||
Hepatocellular carcinoma; Multiple scierosis [ICD9:155, 340; ICD10: C22.0, G35] | |||||
Immune disorder [ICD10: D80-D89] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Multiple scierosis [ICD9: 340; ICD10: G35] | |||||
Macular degeneration [ICD9: 362.5; ICD10: H35.3] | |||||
Primary progressive multiple sclerosis [ICD9: 340; ICD10: G35] | |||||
Psoriasis [ICD9: 696; ICD10: L40] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Function |
G-protein coupled receptorfor the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 andMAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization andbone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3- phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T13852
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UniProt ID | |||||
Sequence |
MGPTSVPLVKAHRSSVSDYVNYDIIVRHYNYTGKLNISADKENSIKLTSVVFILICCFII
LENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTANLLLSGATTYKLTPAQWFLR EGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNNFRLFLLISACWVISLILGGLPIM GWNCISALSSCSTVLPLYHKHYILFCTTVFTLLLLSIVILYCRIYSLVRTRSRRLTFRKN ISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDVGCKVKTCDILFRAEYFLVLA VLNSGTNPIIYTLTNKEMRRAFIRIMSCCKCPSGDSAGKFKRPIIAGMEFSRSKSDNSSH PQKDEGDNPETIMSSGNVNSSS |
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Drugs and Mode of Action | |||||
Drug(s) | Fingolimod | Drug Info | Approved | Primary progressive multiple sclerosis | [531351], [539536] |
BAF312 | Drug Info | Phase 3 | Hepatocellular carcinoma; Multiple scierosis | [524022] | |
RPC-1063 | Drug Info | Phase 3 | Advanced non-small cell lung cancer | [525004] | |
Sphingosine-1-phosphate receptor-1 agonist | Drug Info | Phase 3 | Immune disorder | [551791] | |
ACT-128800 | Drug Info | Phase 2 | Psoriasis | [522598] | |
KRP-203 | Drug Info | Phase 2 | Cutaneous lupus erythematosus | [523356] | |
MT-1303 | Drug Info | Phase 2 | Multiple scierosis | [524345] | |
ONO-4641 | Drug Info | Phase 2 | Rheumatoid arthritis | [523225] | |
ASP-4058 | Drug Info | Phase 1 | Multiple scierosis | [533005] | |
CS-0777 | Drug Info | Phase 1 | Multiple scierosis | [522226] | |
GSK-2018682 | Drug Info | Phase 1 | Immune disorder | [523536] | |
Sonepcizumab | Drug Info | Phase 1 | Macular degeneration | [522296] | |
Sphingosine-1-phosphate | Drug Info | Phase 1 | Acne vulgaris | [523681], [543301] | |
PF-4629991 | Drug Info | Discontinued in Phase 1 | Rheumatoid arthritis | [548892] | |
XL-541 | Drug Info | Terminated | Cancer | [548837] | |
Inhibitor | (3-Tetradecylamino-cyclohexyl)-phosphonic acid | Drug Info | [527193] | ||
(3-Tetradecylamino-cyclopentyl)-phosphonic acid | Drug Info | [527193] | |||
(S)-FTY720P | Drug Info | [530125] | |||
1-(4-nonylbenzyl)azetidine-3-carboxylic acid | Drug Info | [527349] | |||
1-(4-nonylbenzyl)pyrrolidin-3-ylphosphonic acid | Drug Info | [527349] | |||
1-(4-nonylbenzyl)pyrrolidine-3-carboxylic acid | Drug Info | [527349] | |||
3-(N-alkylamino) propylphosphonic acid derivative | Drug Info | [527193] | |||
3-(tetradecylamino)propylphosphonic acid | Drug Info | [527349] | |||
3-amino-5-(4-octylphenyl)pentanoic acid | Drug Info | [530721] | |||
4-amino-6-(4-octylphenyl)hexanoic acid | Drug Info | [530721] | |||
GNF-PF-78 | Drug Info | [531262] | |||
GNF-PF-826 | Drug Info | [531262] | |||
NOX-S91 | Drug Info | [543701] | |||
Sphingosine-1-phosphate | Drug Info | [530799] | |||
[3-(4-Nonyl-benzylamino)-propyl]-phosphonic acid | Drug Info | [527193] | |||
Modulator | ACT-128800 | Drug Info | [543701] | ||
ASP-4058 | Drug Info | [533005] | |||
BAF312 | Drug Info | [532456] | |||
CS-0777 | Drug Info | [531862], [532807] | |||
Fingolimod | Drug Info | [531351], [536837] | |||
KRP-107 | Drug Info | [543701] | |||
MT-1303 | Drug Info | [533299] | |||
NIBR-785 | Drug Info | [543701] | |||
Agonist | AFD(R) | Drug Info | [526319] | ||
AUY954 | Drug Info | [528529] | |||
BMS-520 | Drug Info | [543701] | |||
compound 26 | Drug Info | [527767] | |||
CYM5181 | Drug Info | [529645] | |||
CYM5442 | Drug Info | [529645] | |||
FTY720-phosphate | Drug Info | [526319] | |||
GSK-1842799C | Drug Info | [543701] | |||
GSK-2018682 | Drug Info | [532456] | |||
KRP 203-phosphate | Drug Info | [529067] | |||
KRP-203 | Drug Info | [532341], [532456] | |||
LPA | Drug Info | [534686] | |||
ONO-4641 | Drug Info | [532134], [532456] | |||
PF-4629991 | Drug Info | [551919] | |||
RPC-1063 | Drug Info | [532456] | |||
SEW2871 | Drug Info | [526934] | |||
Sphingosine-1-phosphate receptor-1 agonist | Drug Info | [551792] | |||
Antagonist | AMG-247 | Drug Info | [543701] | ||
NIBR-0213 | Drug Info | [532051] | |||
VPC03090-P | Drug Info | [531499] | |||
VPC23019 | Drug Info | [527334] | |||
VPC44116 | Drug Info | [528528] | |||
W146 | Drug Info | [528303] | |||
XL-541 | Drug Info | [531753] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
Pathways | |||||
KEGG Pathway | FoxO signaling pathway | ||||
Sphingolipid signaling pathway | |||||
Neuroactive ligand-receptor interaction | |||||
NetPath Pathway | IL4 Signaling Pathway | ||||
TGF_beta_Receptor Signaling Pathway | |||||
IL2 Signaling Pathway | |||||
Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | ||||
S1P3 pathway | |||||
S1P1 pathway | |||||
Sphingosine 1-phosphate (S1P) pathway | |||||
PDGFR-beta signaling pathway | |||||
Reactome | G alpha (i) signalling events | ||||
Lysosphingolipid and LPA receptors | |||||
WikiPathways | Signal Transduction of S1P Receptor | ||||
Small Ligand GPCRs | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
GPCRs, Other | |||||
References | |||||
Ref 522226 | ClinicalTrials.gov (NCT00616733) 12-week Safety Evaluation of Oral CS-0777 in Multiple Sclerosis Patients. U.S. National Institutes of Health. | ||||
Ref 522296 | ClinicalTrials.gov (NCT00661414) Safety Study of ASONEP (Sonepcizumab/LT1009) to Treat Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 522598 | ClinicalTrials.gov (NCT00852670) ACT-128800 in Psoriasis. U.S. National Institutes of Health. | ||||
Ref 523225 | ClinicalTrials.gov (NCT01226745) A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis. U.S. National Institutes of Health. | ||||
Ref 523356 | ClinicalTrials.gov (NCT01294774) Safety and Efficacy of KRP203 in Subacute Cutaneous Lupus Erythematosus. U.S. National Institutes of Health. | ||||
Ref 523536 | ClinicalTrials.gov (NCT01387217) GSK2018682 FTIH in Healthy Volunteers. U.S. National Institutes of Health. | ||||
Ref 523681 | ClinicalTrials.gov (NCT01466322) A Study to Assess the Relative Bioavailability of Different Formulations of GSK2018682, a Sphingosine-1-phosphate Receptor Subtype 1 Agonist, in Healthy Volunteers.. U.S. National Institutes of Health. | ||||
Ref 524022 | ClinicalTrials.gov (NCT01665144) Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND). U.S. National Institutes of Health. | ||||
Ref 524345 | ClinicalTrials.gov (NCT01890655) Extension Study of MT-1303. U.S. National Institutes of Health. | ||||
Ref 525004 | ClinicalTrials.gov (NCT02294058) Phase 3 Study of RPC1063 in Relapsing MS. U.S. National Institutes of Health. | ||||
Ref 533005 | ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS One. 2014 Oct 27;9(10):e110819. | ||||
Ref 539536 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2407). | ||||
Ref 543301 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 911). | ||||
Ref 548837 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029368) | ||||
Ref 526319 | The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002 Jun 14;277(24):21453-7. Epub 2002 Apr 19. | ||||
Ref 526934 | Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004 Apr 2;279(14):13839-48. Epub 2004 Jan 19. | ||||
Ref 527193 | Bioorg Med Chem Lett. 2004 Oct 4;14(19):4861-6.Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors. | ||||
Ref 527334 | Sphingosine 1-phosphate analogs as receptor antagonists. J Biol Chem. 2005 Mar 18;280(11):9833-41. Epub 2004 Dec 8. | ||||
Ref 527349 | J Med Chem. 2004 Dec 30;47(27):6662-5.A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists. | ||||
Ref 527767 | Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3. J Med Chem. 2005 Oct 6;48(20):6169-73. | ||||
Ref 528303 | Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006 Aug;2(8):434-41. Epub 2006 Jul 9. | ||||
Ref 528528 | Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg Med Chem. 2007 Jan 15;15(2):663-77. Epub2006 Nov 1. | ||||
Ref 528529 | A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol. 2006 Nov;13(11):1227-34. | ||||
Ref 529067 | A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. J Pharmacol Exp Ther. 2008 Jan;324(1):276-83. Epub 2007 Sep 26. | ||||
Ref 529645 | Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol Pharmacol. 2008 Nov;74(5):1308-18. | ||||
Ref 530125 | Nat Chem Biol. 2009 Jun;5(6):428-34.Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. | ||||
Ref 530721 | Bioorg Med Chem Lett. 2010 Mar 1;20(5):1485-7. Epub 2010 Jan 28.S1P receptor mediated activity of FTY720 phosphate mimics. | ||||
Ref 530799 | Bioorg Med Chem Lett. 2010 Apr 15;20(8):2520-4. Epub 2010 Mar 3.Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists. | ||||
Ref 531262 | Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). | ||||
Ref 531499 | Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther. 2011 Sep;338(3):879-89. | ||||
Ref 531633 | Prevention of ocular scarring after glaucoma filtering surgery using the monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model. J Glaucoma. 2013 Feb;22(2):145-51. | ||||
Ref 531753 | Discovery of a novel class of potent and orally bioavailable sphingosine 1-phosphate receptor 1 antagonists. J Med Chem. 2012 Feb 9;55(3):1368-81. | ||||
Ref 531862 | Pharmacological effects of CS-0777, a selective sphingosine 1-phosphate receptor-1 modulator: results from a 12-week, open-label pilot study in multiple sclerosis patients. J Neuroimmunol. 2012 May 15;246(1-2):100-7. | ||||
Ref 532051 | A potent and selective S1P(1) antagonist with efficacy in experimental autoimmune encephalomyelitis. Chem Biol. 2012 Sep 21;19(9):1142-51. | ||||
Ref 532134 | Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin Exp Immunol. 2013 Jan;171(1):54-62. | ||||
Ref 532341 | KRP-203, sphingosine 1-phosphate receptor type 1 agonist, ameliorates atherosclerosis in LDL-R-/- mice. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1505-12. | ||||
Ref 532456 | Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702. | ||||
Ref 532807 | Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist. ACS Med Chem Lett. 2011 Mar 2;2(5):368-72. | ||||
Ref 533005 | ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS One. 2014 Oct 27;9(10):e110819. | ||||
Ref 533299 | Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis. CNS Drugs. 2015 Jul;29(7):565-75. | ||||
Ref 534686 | Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist. J Biol Chem. 1998 Aug 21;273(34):22105-12. | ||||
Ref 536837 | Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs. 2008 Sep;13(3):465-77. |
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