DAT Inhibitors
5 drugsAbout DAT
The dopamine transporter (DAT), encoded by the SLC6A3 gene, regulates dopamine levels in the brain by removing it from the synapse, thus playing a key role in neuronal signaling.
Human genetic studies provide strong validation for DAT as a therapeutic target, with variants linked to classic dopamine transporter deficiency syndrome (score 0.85) and infantile dystonia-parkinsonism (score 0.83). Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
DAT is targeted by 5 FDA-approved small molecule drugs, including NUVIGIL, PROVIGIL, and IOFLUPANE I-123, developed by companies like CURIUM and NUVO PHARMS, primarily for other therapeutic areas.
DAT Genetic Evidence Strong
Strong genetic evidence supports DAT's role in diseases like dopamine transporter deficiency syndrome.
Strong genetic support increases clinical success probability, favoring DAT activator development.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
15 totalGWAS and other genetic studies link SLC6A3 to 15 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 1 strong
max H4: 0.94eQTL/pQTL signals for SLC6A3 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 DAT Drugs
Four companies, including CURIUM and NUVO PHARMS, have approved drugs targeting DAT.
The presence of established players suggests moderate barriers to entry in the DAT-targeting drug market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| DATSCAN | GE HLTHCARE | 2011 | 2 |
| IOFLUPANE I-123 | CURIUM | 2022 | 2 |
DAT Drug Modality Landscape
Modalities
Routes of Administration
DAT is amenable to small molecule drugs, with oral options available for convenient dosing.
Explore alternative modalities like antibodies or gene therapies to differentiate from existing drugs.
DAT Clinical Trials 132 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on DAT. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 26 | 24 | 1 | 1 | 96% |
| Phase 2 | 44 | 30 | 8 | 6 | 79% |
| Phase 3 | 38 | 19 | 8 | 11 | 70% |
| Phase 4 | 24 | 16 | 5 | 3 | 76% |
Top Sponsors
By Modality
DAT Drug Approval Timeline (1998 - 2022)
The first DAT-targeting drug was approved in 1998, with the most recent in 2022.
The approval timeline indicates continued interest in DAT as a target, but potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 85 (16 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 DAT. A trial counts if an approved drug acting on DAT 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.