Thyroid hormone receptor Modulators
13 drugsAbout Thyroid hormone receptor
The thyroid hormone receptor (THR), encoded by the THRA gene, is a nuclear receptor protein that regulates gene expression in response to thyroid hormones. THR influences various physiological processes, making it a compelling target for drug development.
Human genetic studies provide strong validation for THR as a therapeutic target (max score 0.87). Loss-of-function variants are associated with peripheral resistance to thyroid hormones (score 0.87), suggesting activation may be beneficial.
THR is targeted by 13 FDA-approved small molecule drugs, including CYTOMEL, LEVOTHYROXINE SODIUM, and SYNTHROID. These drugs, developed by 10 companies including PIRAMAL CRITICAL and AbbVie, are all indicated for oncology.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 1 trials.
- phase4 represents biological uncertainty with 42% completion.
Human Genetic Evidence Strong
Genetic evidence strongly supports THR as a drug target, with a maximum score of 0.87.
Strong genetic support suggests that clinical trials targeting THR have a higher probability of success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in endocrine system disease, genetic, familial or congenital disease, nervous system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
8 totalGWAS and other genetic studies link THRA to 8 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for THRA 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 Drugs
Ten companies have approved drugs targeting THR, with PIRAMAL CRITICAL and AbbVie as top players.
The presence of multiple established players suggests a moderately competitive market with potential entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| LEVOLET | GENUS LIFESCIENCES | 2003 | 2 |
| EUTHYROX | EMD SERONO INC | 2002 | 2 |
| SYNTHROID | AbbVie | 2002 | 2 |
| TIROSINT | IBSA | 2006 | 2 |
| ERMEZA | Viatris | 2022 | 2 |
| UNITHROID | STEVENS J | 2000 | 2 |
| LEVOXYL | KING PHARMS | 2001 | 2 |
| TIROSINT-SOL | IBSA | 2016 | 2 |
| THYRO-TABS | ALVOGEN | 2002 | 2 |
| LEVO-T | CEDIPROF INC | 2002 | 2 |
Drug Modality Landscape
Modalities
Routes of Administration
Thyroid hormone receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or fusion proteins could provide a competitive advantage.
Clinical Trials 105 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 29 | 21 | 2 | 6 | 91% |
| Phase 2 | 36 | 23 | 3 | 9 | 88% |
| Phase 3 | 13 | 7 | 1 | 5 | 88% |
| Phase 4 | 27 | 14 | 10 | 3 | 58% |
Top Sponsors
By Modality
Top Conditions
Drug Approval Timeline (1956 - 2022)
The first THR-targeting drug was approved in 1956, with the most recent approval in 2022.
The long approval history indicates a mature market, but recent approvals suggest continued innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 10 companies competing
- • Market share by company
Full Drug Portfolio
- • All 13 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 13-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 75 clinical trials targeting Thyroid hormone receptor.
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