S1PR1 Inhibitors
7 drugsAbout S1PR1
S1PR1 (sphingosine-1-phosphate receptor 1) is a G protein-coupled receptor that modulates immune cell trafficking. It plays a crucial role in lymphocyte egress from lymphoid organs, influencing immune responses. Activation of S1PR1 leads to downstream signaling cascades affecting cell migration and survival.
Human genetics provide moderate support for S1PR1 as a therapeutic target, with associations to hyperaldosteronism (score 0.49) and other diseases. Colocalization analysis reveals 15 strong eQTL/pQTL signals, suggesting a link between S1PR1 expression and disease. These findings support further investigation into S1PR1's role in disease.
S1PR1 is targeted by five FDA-approved small molecule drugs, including GILENYA, MAYZENT, and PONVORY. These drugs are developed by companies like Novartis, CYCLE, and VANDA PHARMS INC. The therapeutic areas span CNS disorders and other indications.
S1PR1 Genetic Evidence Moderate
Genetic evidence offers moderate support for S1PR1, with a max score of 0.49 linked to hyperaldosteronism.
Further research into the genes regulated by S1PR1 could reveal novel therapeutic opportunities.
Evidence Across Diseases
12 totalGWAS and other genetic studies link S1PR1 to 12 diseases.
🔗 Colocalization Evidence 15 strong
max H4: 1.00eQTL/pQTL signals for S1PR1 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 S1PR1 Drugs
Four companies have approved S1PR1-targeting drugs, including Novartis and VANDA PHARMS INC.
The presence of multiple players indicates a competitive market, requiring differentiated strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| MAYZENT | Novartis | 2019 | 3 |
| ZEPOSIA | Bristol-Myers Squibb | 2020 | 2 |
| FINGOLIMOD HYDROCHLORIDE | CHARTWELL RX | 2019 | 1 |
| VELSIPITY | Pfizer | 2023 | 1 |
S1PR1 Drug Modality Landscape
Modalities
Routes of Administration
S1PR1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage.
S1PR1 Clinical Trials 105 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on S1PR1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 18 | 16 | 1 | 1 | 94% |
| Phase 2 | 33 | 15 | 9 | 9 | 63% |
| Phase 3 | 30 | 14 | 8 | 8 | 64% |
| Phase 4 | 24 | 13 | 7 | 4 | 65% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved S1PR1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting S1PR1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
S1PR1 Drug Approval Timeline (2010 - 2023)
The first S1PR1 drug was approved in 2010 (GILENYA), with the most recent in 2021 (PONVORY).
The steady approval rate suggests continued interest in S1PR1, but also increasing market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 38 (13 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 S1PR1. A trial counts if an approved drug acting on S1PR1 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.