SERT Inhibitors
9 drugsAbout SERT
The serotonin transporter (SERT), also known as 5-HTT, regulates serotonergic neurotransmission by reuptaking serotonin from the synaptic cleft. This process controls the duration and intensity of serotonin signaling, impacting various neurological functions.
SERT is a therapeutic target in the CNS, with moderate genetic evidence (max score 0.54) linking it to obsessive-compulsive disorder and insomnia. Loss-of-function variants appear protective, suggesting that SERT inhibition may be beneficial for these conditions.
Nine FDA-approved small molecule drugs target SERT, including VENLAFAXINE HYDROCHLORIDE, EFFEXOR XR, and PRISTIQ. These drugs, developed by companies like MEDICAP LABS and UPJOHN, are used to treat CNS disorders.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 80% attractiveness score.
- White space opportunity in Bladder Cancer with only 1 trials.
SERT Genetic Evidence Moderate
Genetic evidence provides moderate support for SERT as a drug target (max score 0.54).
Further investigation of SERT's role in OCD and insomnia could reveal novel therapeutic strategies.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 2 traits
- • Strong signal in nervous system disease, psychiatric disorder, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
8 totalGWAS and other genetic studies link SLC6A4 to 8 diseases.
Inhibiting this target may be therapeutic
Inhibiting this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 0.99eQTL/pQTL signals for SLC6A4 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 SERT Drugs
Eight companies have approved drugs targeting SERT, with MEDICAP LABS and UPJOHN among the leaders.
The presence of multiple established players suggests a competitive market, requiring a strong value proposition for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| VILAZODONE HYDROCHLORIDE | INVAGEN PHARMS | 2019 | 1 |
| RALDESY | KAMAT | 2024 | 1 |
| LEVOMILNACIPRAN HYDROCHLORIDE | Hikma | 2019 | 1 |
| PRISTIQ | PF PRISM CV | 2008 | 1 |
| FETZIMA | AbbVie | 2013 | 1 |
| VIIBRYD | AbbVie | 2011 | 1 |
SERT Drug Modality Landscape
Modalities
Routes of Administration
SERT is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or gene therapies could provide differentiation in the SERT market.
SERT Clinical Trials 160 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 35 | 29 | 2 | 3 | 94% |
| Phase 2 | 25 | 14 | 5 | 6 | 74% |
| Phase 3 | 39 | 31 | 5 | 3 | 86% |
| Phase 4 | 61 | 42 | 14 | 5 | 75% |
Top Sponsors
By Modality
Top Conditions
SERT Drug Approval Timeline (1997 - 2024)
The first SERT-targeting drug was approved in 1997, with the most recent approval in 2024.
The continued approval of SERT-targeting drugs indicates sustained interest, but also suggests potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 companies competing
- • Market share by company
Full Drug Portfolio
- • All 9 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 9-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 100 clinical trials targeting SERT.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities