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.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Cognition with only 2 trials.
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 |
|---|---|---|---|
| SUNOSI | AXSOME MALTA | 2019 | 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 125 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 25 | 22 | 1 | 2 | 96% |
| Phase 2 | 43 | 30 | 8 | 5 | 79% |
| Phase 3 | 34 | 19 | 8 | 6 | 70% |
| Phase 4 | 23 | 16 | 5 | 1 | 76% |
Top Sponsors
By Modality
Top Conditions
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
- • 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 67 clinical trials targeting DAT.
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