5-HT3R Inhibitors
4 drugsAbout 5-HT3R
The 5-HT3 receptor (5-HT3R), also known as the serotonin receptor subtype 3, is a ligand-gated ion channel crucial in neuronal signaling. It mediates fast synaptic transmission in the central and peripheral nervous systems.
Human genetic studies provide moderate support for 5-HT3R as a therapeutic target, with variants linked to hypermobility syndrome (score 0.38). Higher receptor activity is associated with increased disease risk, suggesting that antagonists may be beneficial.
5-HT3R is targeted by 4 FDA-approved small molecule drugs, including AKYNZEO, SUSTOL, ALOSETRON HYDROCHLORIDE and ONDANSETRON HYDROCHLORIDE. These drugs are utilized across various therapeutic areas categorized as 'other'.
5-HT3R Genetic Evidence Moderate
Genetic evidence offers moderate support, with a maximum score of 0.38 for hypermobility syndrome.
Further investigation into the genetic associations could reveal novel therapeutic opportunities.
Evidence Across Diseases
4 totalGWAS and other genetic studies link HTR3A to 4 diseases.
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 5-HT3R Drugs
Four companies have approved drugs targeting 5-HT3R, including Hikma and HELSINN HLTHCARE.
The relatively low number of players suggests a moderately concentrated market with potential entry opportunities.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| SUSTOL | HERON THERAPS INC | 2016 | 2 |
5-HT3R Drug Modality Landscape
Modalities
Routes of Administration
Only one approved drug targets 5-HT3R, using small molecule modality.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage.
5-HT3R Clinical Trials 176 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on 5-HT3R. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 31 | 26 | 5 | 0 | 84% |
| Phase 2 | 54 | 38 | 10 | 6 | 79% |
| Phase 3 | 43 | 37 | 4 | 2 | 90% |
| Phase 4 | 48 | 37 | 4 | 7 | 90% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
5-HT3R Drug Approval Timeline (2014 - 2014)
The first drug was approved in 2006 (ONDANSETRON HYDROCHLORIDE), and the most recent in 2016 (SUSTOL).
The approval timeline indicates a potentially maturing market with limited recent innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 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: 121 (25 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 5-HT3R. A trial counts if an approved drug acting on 5-HT3R 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.