Protein / target

Sphingosine 1-phosphate receptor 1

Encoded byS1PR1P21453Homo sapiensSwiss-Prot

UniProt: P21453 Ensembl: ENSG00000170989 HGNC: HGNC:3165 NCBI Gene: 1901

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Approved Drug

Protein at a glance

Biological role

Sphingosine-1-phosphate receptor

Strongest disease association

Hypothyroidism

Via encoding gene S1PR1 · Genetic evidence · score 0.55

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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. 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 (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

Subcellular location

Cell membraneEndosomeMembrane raft

Domains and Gene Ontology detail (35)

Gene Ontology

Ccytoplasm
Cendosome
Cexternal side of plasma membrane
Cmembrane raft
Cplasma membrane
Cpresynapse
FG protein-coupled receptor activity
FG protein-coupled receptor binding
Fsphingolipid binding
Fsphingosine-1-phosphate receptor activity
Pactin cytoskeleton organization
Padenylate cyclase-activating G protein-coupled receptor signaling pathway

382 aa · 43 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell migrationUniProt · GOG protein-coupled signallingUniProt · GOImmune signallingGO · Reactome

View supporting evidence

Cell migration

·G protein-coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S…
·cell migration
·chemotaxis
·positive regulation of cell migration

G protein-coupled signalling

·G protein-coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S…
·G protein-coupled receptor activity
·G protein-coupled receptor binding
·adenylate cyclase-activating G protein-coupled receptor signaling pathway

Immune signalling

·T cell migration
·Interleukin-4 and Interleukin-13 signaling

View underlying pathways (3)

Lysosphingolipid and LPA receptors

Interleukin-4 and Interleukin-13 signaling

Potential therapeutics for SARS

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Multiple Sclerosis2 medicines

Fingolimod Hydrochloride ponesimod

Multiple Sclerosis, Relapsing-Remitting2 medicines

Fingolimod Hydrochloride ponesimod

10 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

ponesimod

Narrow target profileApprovedAgonist

Sphingosine 1-phosphate receptor Edg-1 agonist

Indicated for Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Direct interaction with this protein · Only this protein recorded as a target

Fingolimod Hydrochloride

ApprovedAgonist

Sphingosine 1-phosphate receptor agonist

Indicated for Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

Acts on a complex — shared with S1PR5, S1PR2, S1PR4 +1 more · 1 of 5 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene S1PR1

Gene-level evidence surfaced through the gene S1PR1 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Multiple Sclerosis

0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Colitis, Ulcerative

0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Multiple Sclerosis, Relapsing-Remitting

0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

Multiple Sclerosis, Chronic Progressive

0.58Moderately supported

Clinical evidence dominant · Open Targets 0.46

Hypothyroidism

0.55Moderately supported

Genetic evidence dominant · Open Targets 0.33

View evidence synthesis (5)

Multiple SclerosisWell supported

0.75

agreement 0.60–0.91

Clinical96%Literature4%

Open Targets aggregate 0.61 · 2 independent evidence families

Colitis, UlcerativeModerately supported

0.72

agreement 0.58–0.85

Clinical96%Literature3%RNA expression2%

Open Targets aggregate 0.58 · 3 independent evidence families

Multiple Sclerosis, Relapsing-RemittingModerately supported

0.70

agreement 0.55–0.86

Clinical96%Literature4%

Open Targets aggregate 0.57 · 2 independent evidence families

Multiple Sclerosis, Chronic ProgressiveModerately supported

0.58

agreement 0.42–0.73

Clinical97%Literature3%

Open Targets aggregate 0.46 · 2 independent evidence families

HypothyroidismModerately supported

0.55

agreement 0.43–0.67

Genetic100%

Open Targets aggregate 0.33 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Multiple Sclerosis0.61

Colitis, Ulcerative0.58

Multiple Sclerosis, Relapsing-Remitting0.57

Multiple Sclerosis, Chronic Progressive0.46

Lupus Erythematosus, Systemic0.40

Crohn's Disease0.39

Hypothyroidism0.33

Drug development

14 compounds recorded · 10 approved · 4 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

CENERIMODPhase 3

AMISELIMOD HYDROCHLORIDEPhase 2

AMISELIMODPhase 2

SIPONIMODApproval

ETRASIMODApproval

PONESIMODApproval

ETRASIMOD ARGININEApproval

OZANIMOD HYDROCHLORIDEApproval

OZANIMODApproval

FINGOLIMODApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ponesimod in Patients With Moderately to Severely Active Ulcerative ColitisPHASE3

NOT_YET_RECRUITING · via ponesimod · NCT07686081

Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot TrialPHASE1

COMPLETED · via Fingolimod Hydrochloride · NCT03941743

A Multicenter, Open Label Study to Investigate the Safety and Efficacy of Ponesimod in the Treatment of Moderate-to-Severe Chronic Plaque PsoriasisPHASE3

RECRUITING · via ponesimod · NCT07362017

Multicenter, Non-comparative Extension of Study AC-058B301, to Investigate the Long-term Safety, Tolerability, and Control of Disease of Ponesimod 20 mg in Subjects With Relapsing Multiple SclerosisPHASE3

COMPLETED · via ponesimod · NCT03232073

View all trials (8)

Multicenter, Randomized, Double-blind, Parallel-group, add-on, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®)PHASE3

TERMINATED · via ponesimod · NCT02907177

Multicenter, Randomized, Double-blind, Parallel-group, Active-controlled, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Teriflunomide in Subjects With Relapsing Multiple SclerosisPHASE3

COMPLETED · via ponesimod · NCT02425644

A Phase 2, Open-label, Single-arm, Intra-subject Dose-escalation Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of Ponesimod in Subjects With Symptomatic Moderate or Severe Chronic GVHD Inadequately Responding to First or Second Line TherapyPHASE2

TERMINATED · via ponesimod · NCT02461134

Multicenter, Randomized, Double-blind, Parallel-group Extension to Study AC-058B201 to Investigate the Long-term Safety, Tolerability, and Efficacy of Three Doses of Ponesimod, an Oral S1P1 Receptor Agonist, in Patients With Relapsing-remitting Multiple SclerosisPHASE2

COMPLETED · via ponesimod · NCT01093326

A Phase 1, Open-label, Parallel-group Study to Assess the Effect of Steady-state Carbamazepine on the Pharmacokinetics of Ponesimod in Healthy Adult ParticipantsPHASE1

COMPLETED · via ponesimod · NCT05552196

Treatment of Established Chemotherapy-Induced Neuropathy With Fingolimod: A Pilot TrialEARLY_PHASE1

COMPLETED · via Fingolimod Hydrochloride · NCT03943498

Single-center, Open-label, Randomized, Two-way Crossover Study to Investigate the Absolute Bioavailability of a Single Oral Dose of Ponesimod in Healthy Male SubjectsPHASE1

COMPLETED · via ponesimod · NCT02068235

A Single-center, Double-blind, Randomized, Placebo- and Positive-controlled, Parallel-group, Multiple-dose, Up-titration Study of the Electrocardiographic Effects of Ponesimod in Healthy Male and Female SubjectsPHASE1

COMPLETED · via ponesimod · NCT02136888

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

New publication2023-09-05
Glial Sphingosine-Mediated Epigenetic Regulation Stabilizes Synaptic Function in <i>Drosophila</i> Models of Alzheimer's Disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023 · 8 citations · Europe PMC · via Fingolimod Hydrochloride
Regulatory approval2021-05-19
Approval: Ponvory (EMA)
ema · regulatory · ema · via ponesimod
Regulatory approval2020-06-25
Approval: Fingolimod Accord (EMA)
ema · regulatory · ema · via Fingolimod Hydrochloride
Regulatory approval2011-03-17
Approval: Gilenya (EMA)
ema · regulatory · ema · via Fingolimod Hydrochloride

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.