SERT Inhibitors
17 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.
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 |
|---|---|---|---|
| VENLAFAXINE HYDROCHLORIDE | ORBION PHARMS | 2006 | 4 |
| EFFEXOR XR | UPJOHN | 1997 | 4 |
| PAXIL CR | Apotex | 1999 | 4 |
| TRAMADOL HYDROCHLORIDE | STRIDES PHARMA INTL | 2002 | 1 |
| LEVOMILNACIPRAN HYDROCHLORIDE | AMNEAL PHARMS | 2019 | 1 |
| FLUVOXAMINE MALEATE | APPCO | 2000 | 1 |
| TRINTELLIX | Takeda | 2013 | 1 |
| VILAZODONE HYDROCHLORIDE | Teva | 2019 | 1 |
| FETZIMA | AbbVie | 2013 | 1 |
| PRISTIQ | PF PRISM CV | 2008 | 1 |
| NORPRAMIN | VALIDUS PHARMS | 1964 | 1 |
| RALDESY | KAMAT | 2024 | 1 |
| VIIBRYD | AbbVie | 2011 | 1 |
| SAVELLA | AbbVie | 2009 | 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 631 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on SERT. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 117 | 105 | 2 | 9 | 98% |
| Phase 2 | 135 | 85 | 26 | 20 | 77% |
| Phase 3 | 175 | 122 | 27 | 26 | 82% |
| Phase 4 | 204 | 144 | 35 | 24 | 80% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
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
- • 15 companies competing
- • Market share by company
Full Drug Portfolio
- • All 17 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 17-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 362 (90 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 SERT. A trial counts if an approved drug acting on SERT 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.