Target Information
| Target General Information | Top | |||||
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| Target ID |
T13852
(Former ID: TTDC00258)
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| Target Name |
Sphingosine-1-phosphate receptor 1 (S1PR1)
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| Synonyms |
Sphingosine 1-phosphate receptor Edg-1; S1P1; S1P receptor Edg-1; S1P receptor 1; Endothelial differentiation G-protein coupled receptor 1; CHEDG1; CD363
Click to Show/Hide
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| Gene Name |
S1PR1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Multiple sclerosis [ICD-11: 8A40] | |||||
| 2 | Ulcerative colitis [ICD-11: DD71] | |||||
| Function |
Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP 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 and bone homeostasis. 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. G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MGPTSVPLVKAHRSSVSDYVNYDIIVRHYNYTGKLNISADKENSIKLTSVVFILICCFII
LENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTANLLLSGATTYKLTPAQWFLR EGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNNFRLFLLISACWVISLILGGLPIM GWNCISALSSCSTVLPLYHKHYILFCTTVFTLLLLSIVILYCRIYSLVRTRSRRLTFRKN ISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDVGCKVKTCDILFRAEYFLVLA VLNSGTNPIIYTLTNKEMRRAFIRIMSCCKCPSGDSAGKFKRPIIAGMEFSRSKSDNSSH PQKDEGDNPETIMSSGNVNSSS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T12CH9 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | Etrasimod | Drug Info | Approved | Ulcerative colitis | [2] | |
| 2 | Fingolimod | Drug Info | Approved | Primary progressive multiple sclerosis | [1], [3] | |
| 3 | Ozanimod | Drug Info | Approved | Multiple sclerosis | [4] | |
| 4 | Ponesimod | Drug Info | Approved | Multiple sclerosis | [5] | |
| 5 | Siponimod | Drug Info | Approved | Multiple sclerosis | [6] | |
| Clinical Trial Drug(s) | [+] 12 Clinical Trial Drugs | + | ||||
| 1 | CBP-307 | Drug Info | Phase 2 | Ulcerative colitis | [7] | |
| 2 | KRP-203 | Drug Info | Phase 2 | Cutaneous lupus erythematosus | [8] | |
| 3 | MT-1303 | Drug Info | Phase 2 | Multiple sclerosis | [9] | |
| 4 | ONO-4641 | Drug Info | Phase 2 | Rheumatoid arthritis | [10] | |
| 5 | VTX-002 | Drug Info | Phase 2 | Ulcerative colitis | [11] | |
| 6 | ASP-4058 | Drug Info | Phase 1 | Multiple sclerosis | [12] | |
| 7 | BMS-986104 | Drug Info | Phase 1 | Rheumatoid arthritis | [13] | |
| 8 | CS-0777 | Drug Info | Phase 1 | Multiple sclerosis | [14] | |
| 9 | GSK-2018682 | Drug Info | Phase 1 | Immune System disease | [15] | |
| 10 | SAR247799 | Drug Info | Phase 1 | Cardiovascular disease | [16] | |
| 11 | Sonepcizumab | Drug Info | Phase 1 | Macular degeneration | [17] | |
| 12 | Sphingosine-1-phosphate | Drug Info | Phase 1 | Acne vulgaris | [18], [19] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | PF-4629991 | Drug Info | Discontinued in Phase 1 | Rheumatoid arthritis | [20] | |
| 2 | XL-541 | Drug Info | Terminated | Solid tumour/cancer | [21] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 19 Agonist drugs | + | ||||
| 1 | Etrasimod | Drug Info | [2] | |||
| 2 | Ozanimod | Drug Info | [4] | |||
| 3 | Ponesimod | Drug Info | [5] | |||
| 4 | CBP-307 | Drug Info | [23] | |||
| 5 | KRP-203 | Drug Info | [24], [25] | |||
| 6 | ONO-4641 | Drug Info | [24], [27] | |||
| 7 | GSK-2018682 | Drug Info | [24] | |||
| 8 | SAR247799 | Drug Info | [16] | |||
| 9 | PF-4629991 | Drug Info | [34] | |||
| 10 | AFD(R) | Drug Info | [40] | |||
| 11 | AUY954 | Drug Info | [42] | |||
| 12 | BMS-520 | Drug Info | [41] | |||
| 13 | CYM5181 | Drug Info | [43] | |||
| 14 | CYM5442 | Drug Info | [43] | |||
| 15 | FTY720-phosphate | Drug Info | [40] | |||
| 16 | GSK-1842799C | Drug Info | [41] | |||
| 17 | KRP 203-phosphate | Drug Info | [45] | |||
| 18 | LPA | Drug Info | [46] | |||
| 19 | SEW2871 | Drug Info | [48] | |||
| Modulator | [+] 9 Modulator drugs | + | ||||
| 1 | Fingolimod | Drug Info | [1], [22] | |||
| 2 | Siponimod | Drug Info | [6] | |||
| 3 | MT-1303 | Drug Info | [26] | |||
| 4 | VTX-002 | Drug Info | [28] | |||
| 5 | ASP-4058 | Drug Info | [12] | |||
| 6 | BMS-986104 | Drug Info | [13] | |||
| 7 | CS-0777 | Drug Info | [29], [30] | |||
| 8 | KRP-107 | Drug Info | [41] | |||
| 9 | NIBR-785 | Drug Info | [41] | |||
| Inhibitor | [+] 15 Inhibitor drugs | + | ||||
| 1 | Sphingosine-1-phosphate | Drug Info | [33] | |||
| 2 | (3-Tetradecylamino-cyclohexyl)-phosphonic acid | Drug Info | [36] | |||
| 3 | (3-Tetradecylamino-cyclopentyl)-phosphonic acid | Drug Info | [36] | |||
| 4 | (S)-FTY720P | Drug Info | [37] | |||
| 5 | 1-(4-nonylbenzyl)azetidine-3-carboxylic acid | Drug Info | [38] | |||
| 6 | 1-(4-nonylbenzyl)pyrrolidin-3-ylphosphonic acid | Drug Info | [38] | |||
| 7 | 1-(4-nonylbenzyl)pyrrolidine-3-carboxylic acid | Drug Info | [38] | |||
| 8 | 3-(N-alkylamino) propylphosphonic acid derivative | Drug Info | [36] | |||
| 9 | 3-(tetradecylamino)propylphosphonic acid | Drug Info | [38] | |||
| 10 | 3-amino-5-(4-octylphenyl)pentanoic acid | Drug Info | [39] | |||
| 11 | 4-amino-6-(4-octylphenyl)hexanoic acid | Drug Info | [39] | |||
| 12 | GNF-PF-78 | Drug Info | [44] | |||
| 13 | GNF-PF-826 | Drug Info | [44] | |||
| 14 | NOX-S91 | Drug Info | [41] | |||
| 15 | [3-(4-Nonyl-benzylamino)-propyl]-phosphonic acid | Drug Info | [36] | |||
| Antagonist | [+] 7 Antagonist drugs | + | ||||
| 1 | XL-541 | Drug Info | [35] | |||
| 2 | AMG-247 | Drug Info | [41] | |||
| 3 | NIBR-0213 | Drug Info | [47] | |||
| 4 | VPC03090-P | Drug Info | [49] | |||
| 5 | VPC23019 | Drug Info | [50] | |||
| 6 | VPC44116 | Drug Info | [51] | |||
| 7 | W146 | Drug Info | [52] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Ozanimod | Ligand Info | |||||
| Structure Description | Cryo-EM structure of ozanimod -bound Sphingosine-1-phosphate receptor 1 in complex with Gi protein | PDB:7EW0 | ||||
| Method | Electron microscopy | Resolution | 3.42 Å | Mutation | No | [53] |
| PDB Sequence |
YDIIVRHYNY
31 TGKLTSVVFI53 LICCFIILEN63 IFVLLTIWKT73 KKFHRPMYYF83 IGNLALSDLL 93 AGVAYTANLL103 LSGATTYKLT113 PAQWFLREGS123 MFVALSASVF133 SLLAIAIERY 143 ITMLKMKLHN153 GSNNFRLFLL163 ISACWVISLI173 LGGLPIMGWN183 CISALSSCST 193 VLPLYHKHYI203 LFCTTVFTLL213 LLSIVILYCR223 IYSLVRTRSR233 RLTFRKSEKS 251 LALLKTVIIV261 LSVFIACWAP271 LFILLLLDVG281 CKVKTCDILF291 RAEYFLVLAV 301 LNSGTNPIIY311 TLTNKEMRRA321 FIRI
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LYS34
2.543
ASN101
4.479
GLU121
3.453
MET124
3.486
PHE125
3.134
LEU128
3.660
SER129
3.065
VAL132
4.559
VAL194
3.323
LEU195
3.332
ILE203
4.435
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| Ligand Name: Cenerimod | Ligand Info | |||||
| Structure Description | Cryo-EM structure of cenerimod -bound Sphingosine-1-phosphate receptor 1 in complex with Gi protein | PDB:7EVZ | ||||
| Method | Electron microscopy | Resolution | 3.07 Å | Mutation | No | [53] |
| PDB Sequence |
YDIIVRHYNY
31 TGKLTSVVFI53 LICCFIILEN63 IFVLLTIWKT73 KKFHRPMYYF83 IGNLALSDLL 93 AGVAYTANLL103 LSGATTYKLT113 PAQWFLREGS123 MFVALSASVF133 SLLAIAIERY 143 ITMLKMKLHN153 GSNNFRLFLL163 ISACWVISLI173 LGGLPIMGWN183 CISALSSCST 193 VLPLYHKHYI203 LFCTTVFTLL213 LLSIVILYCR223 IYSLVRTRSR233 RLTFRKNISE 249 KSLALLKTVI259 IVLSVFIACW269 APLFILLLLD279 VGCKVKTCDI289 LFRAEYFLVL 299 AVLNSGTNPI309 IYTLTNKEMR319 RAFIRI
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LYS34
2.280
ASN101
4.030
SER105
4.754
GLU121
2.688
MET124
3.608
PHE125
2.769
LEU128
3.659
SER129
3.218
VAL132
3.992
PHE133
4.796
LEU174
4.122
VAL194
3.007
LEU195
4.135
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Sphingolipid signaling pathway | hsa04071 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.52E-04 |
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| Closeness centrality | 2.33E-01 | Radiality | 1.41E+01 | Clustering coefficient | 3.33E-01 |
| Neighborhood connectivity | 8.23E+01 | Topological coefficient | 2.86E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | FoxO signaling pathway | |||||
| 2 | Sphingolipid signaling pathway | |||||
| 3 | Neuroactive ligand-receptor interaction | |||||
| NetPath Pathway | [+] 3 NetPath Pathways | + | ||||
| 1 | IL4 Signaling Pathway | |||||
| 2 | TGF_beta_Receptor Signaling Pathway | |||||
| 3 | IL2 Signaling Pathway | |||||
| PID Pathway | [+] 5 PID Pathways | + | ||||
| 1 | Fc-epsilon receptor I signaling in mast cells | |||||
| 2 | S1P3 pathway | |||||
| 3 | S1P1 pathway | |||||
| 4 | Sphingosine 1-phosphate (S1P) pathway | |||||
| 5 | PDGFR-beta signaling pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | G alpha (i) signalling events | |||||
| 2 | Lysosphingolipid and LPA receptors | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | Signal Transduction of S1P Receptor | |||||
| 2 | Small Ligand GPCRs | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| 5 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216956 | |||||
| REF 3 | URL: 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 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021 | |||||
| REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019 | |||||
| REF 7 | ClinicalTrials.gov (NCT04700449) A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC). U.S.National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT01294774) Safety and Efficacy of KRP203 in Subacute Cutaneous Lupus Erythematosus. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT01890655) Extension Study of MT-1303. U.S. National Institutes of Health. | |||||
| REF 10 | 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 11 | ClinicalTrials.gov (NCT05156125) A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects With Moderately to Severely Active Ulcerative Colitis. U.S.National Institutes of Health. | |||||
| REF 12 | 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 13 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 14 | ClinicalTrials.gov (NCT00616733) 12-week Safety Evaluation of Oral CS-0777 in Multiple Sclerosis Patients. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT01387217) GSK2018682 FTIH in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 16 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 17 | ClinicalTrials.gov (NCT00661414) Safety Study of ASONEP (Sonepcizumab/LT1009) to Treat Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 18 | URL: 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 19 | 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 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030004) | |||||
| REF 21 | 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 22 | Emerging oral drugs for multiple sclerosis. Expert Opin Emerg Drugs. 2008 Sep;13(3):465-77. | |||||
| REF 23 | Clinical pipeline report, company report or official report of Connect Biopharma | |||||
| REF 24 | Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702. | |||||
| REF 25 | 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 26 | Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis. CNS Drugs. 2015 Jul;29(7):565-75. | |||||
| REF 27 | 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 28 | Clinical pipeline report, company report or official report of Ventyx Biosciences | |||||
| REF 29 | Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist. ACS Med Chem Lett. 2011 Mar 2;2(5):368-72. | |||||
| REF 30 | 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 31 | National Cancer Institute Drug Dictionary (drug id 595163). | |||||
| REF 32 | 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 33 | Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2520-4. | |||||
| REF 34 | US patent application no. 2010,0158,905, Combination therapy of arthritis with tranilast. | |||||
| REF 35 | 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 36 | Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) rec... Bioorg Med Chem Lett. 2004 Oct 4;14(19):4861-6. | |||||
| REF 37 | Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol. 2009 Jun;5(6):428-34. | |||||
| REF 38 | A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 re... J Med Chem. 2004 Dec 30;47(27):6662-5. | |||||
| REF 39 | S1P receptor mediated activity of FTY720 phosphate mimics. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1485-7. | |||||
| REF 40 | The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002 Jun 14;277(24):21453-7. | |||||
| REF 41 | URL: 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. (Target id: 275). | |||||
| REF 42 | 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 43 | 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 44 | In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. | |||||
| REF 45 | A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-d... J Pharmacol Exp Ther. 2008 Jan;324(1):276-83. | |||||
| REF 46 | 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 47 | A potent and selective S1P(1) antagonist with efficacy in experimental autoimmune encephalomyelitis. Chem Biol. 2012 Sep 21;19(9):1142-51. | |||||
| REF 48 | 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. | |||||
| REF 49 | Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther. 2011 Sep;338(3):879-89. | |||||
| REF 50 | Sphingosine 1-phosphate analogs as receptor antagonists. J Biol Chem. 2005 Mar 18;280(11):9833-41. | |||||
| REF 51 | 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. | |||||
| REF 52 | 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. | |||||
| REF 53 | Structures of signaling complexes of lipid receptors S1PR1 and S1PR5 reveal mechanisms of activation and drug recognition. Cell Res. 2021 Dec;31(12):1263-1274. | |||||
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