S1PR5 Inhibitors
6 drugsAbout S1PR5
S1PR5 is a G protein-coupled receptor (GPCR) involved in cell signaling pathways. It plays a role in various physiological processes, including immune cell trafficking and central nervous system function.
Human genetic studies provide moderate support for S1PR5 as a therapeutic target, with variants linked to abnormal nasolacrimal system morphology (score 0.36) and response to statins (score 0.34). Colocalization analysis reveals 10 strong eQTL/pQTL signals, suggesting potential regulatory mechanisms.
S1PR5 is targeted by four FDA-approved small molecule drugs, including GILENYA, MAYZENT, and TASCENSO ODT. These drugs are indicated for central nervous system (CNS) disorders and other therapeutic areas.
S1PR5 Genetic Evidence Moderate
Genetic evidence offers moderate support for S1PR5, with a maximum score of 0.36.
Further research is needed to validate the causal link between S1PR5 variants and disease, potentially increasing confidence in target selection.
Evidence Across Diseases
5 totalGWAS and other genetic studies link S1PR5 to 5 diseases.
🔗 Colocalization Evidence 10 strong
max H4: 0.99eQTL/pQTL signals for S1PR5 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 S1PR5 Drugs
Three companies, including Novartis and CYCLE, have approved drugs targeting S1PR5.
The presence of established players like Novartis suggests high barriers to entry, requiring strong differentiation for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ZEPOSIA | Bristol-Myers Squibb | 2020 | 2 |
| FINGOLIMOD HYDROCHLORIDE | CHARTWELL RX | 2019 | 1 |
| VELSIPITY | Pfizer | 2023 | 1 |
S1PR5 Drug Modality Landscape
Modalities
Routes of Administration
S1PR5 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides could offer differentiation in a crowded small molecule space.
S1PR5 Clinical Trials 94 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on S1PR5. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 14 | 12 | 1 | 1 | 92% |
| Phase 2 | 31 | 14 | 8 | 9 | 64% |
| Phase 3 | 25 | 12 | 7 | 6 | 63% |
| Phase 4 | 24 | 13 | 7 | 4 | 65% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved S1PR5 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting S1PR5. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
S1PR5 Drug Approval Timeline (2010 - 2023)
The first S1PR5-targeting drug was approved in 2010, with the most recent approval in 2021.
The approval timeline indicates continued interest in S1PR5 modulation, but potential market saturation warrants careful consideration.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 35 (10 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 S1PR5. A trial counts if an approved drug acting on S1PR5 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.