S1PR4 Inhibitors
4 drugsAbout S1PR4
S1PR4, or sphingosine-1-phosphate receptor 4, is a G protein-coupled receptor involved in modulating immune cell trafficking and inflammation. It functions as a receptor for sphingosine-1-phosphate, a bioactive lipid mediator.
Human genetic studies provide moderate support for S1PR4 as a therapeutic target, with variants linked to severe acute respiratory syndrome (score 0.55) and hypothyroidism (score 0.54). Colocalization analysis reveals 10 strong eQTL/pQTL signals, suggesting potential regulatory roles.
S1PR4 is targeted by 3 FDA-approved small molecule drugs, including GILENYA and TASCENSO ODT. These drugs are primarily used in the central nervous system, with some applications in other therapeutic areas.
S1PR4 Genetic Evidence Moderate
Genetic evidence offers moderate support for S1PR4, with a max score of 0.55.
Further investigation of high H4 colocalization signals may reveal novel therapeutic opportunities.
Evidence Across Diseases
9 totalGWAS and other genetic studies link S1PR4 to 9 diseases.
🔗 Colocalization Evidence 10 strong
max H4: 1.00eQTL/pQTL signals for S1PR4 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top S1PR4 Drugs
The competitive landscape includes 3 companies with approved drugs, such as Novartis and CYCLE.
The relatively low number of players suggests a market with moderate barriers to entry.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| FINGOLIMOD HYDROCHLORIDE | CHARTWELL RX | 2019 | 1 |
S1PR4 Drug Modality Landscape
Modalities
Routes of Administration
S1PR4 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could provide a competitive advantage.
S1PR4 Clinical Trials 65 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on S1PR4. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 5 | 3 | 1 | 1 | 75% |
| Phase 2 | 23 | 12 | 5 | 6 | 71% |
| Phase 3 | 16 | 7 | 3 | 6 | 70% |
| Phase 4 | 21 | 13 | 5 | 3 | 72% |
Top Sponsors
By Modality
Top Conditions
S1PR4 Drug Approval Timeline (2010 - 2023)
The first drug was approved in 2010, with the most recent approval in 2021, spanning 12 years.
The approval timeline indicates continued interest, but potential saturation warrants careful market analysis.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 28 (9 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on S1PR4. A trial counts if an approved drug acting on S1PR4 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.