Thymidylate Synthase Inhibitors
9 drugsAbout Thymidylate Synthase
Thymidylate Synthase (TS) is a crucial enzyme in DNA biosynthesis, catalyzing the methylation of dUMP to dTMP, essential for DNA replication and repair. Inhibiting TS disrupts DNA synthesis, particularly in rapidly dividing cells.
Human genetic studies provide strong validation for TYMS as a therapeutic target (max score 0.82), with loss-of-function variants associated with dyskeratosis congenita. Activation of TYMS is likely beneficial based on genetic evidence.
TS is targeted by 9 FDA-approved drugs, including CAPECITABINE, VYKOURA, and PEMETREXED DISODIUM, all of which are small molecules. These drugs are primarily used in oncology.
Thymidylate Synthase Genetic Evidence Strong
TYMS has strong genetic support with a max score of 0.82 linked to dyskeratosis congenita.
Strong genetic support suggests that TYMS-targeting drugs may have a higher probability of clinical success.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in genetic, familial or congenital disease, cancer or benign tumor, integumentary system disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link TYMS to 6 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 TYMS 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 Thymidylate Synthase Drugs
Eight companies have approved drugs targeting TS, with QILU PHARM HAINAN and AVYXA HOLDINGS among the top players.
The competitive landscape indicates moderate market concentration, suggesting potential entry barriers for new companies.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| PEMETREXED DISODIUM | Apotex | 2022 | 2 |
| PEMFEXY | EAGLE PHARMS | 2020 | 2 |
| AXTLE | AVYXA HOLDINGS | 2024 | 2 |
| PEMETREXED | SHILPA | 2020 | 2 |
| ALIMTA | Eli Lilly | 2004 | 2 |
| PEMETREXED FOR INJECTION | Dr. Reddy's | - | - |
Thymidylate Synthase Drug Modality Landscape
Modalities
Routes of Administration
Thymidylate Synthase is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity to explore alternative modalities like antibodies or fusion proteins.
Thymidylate Synthase Clinical Trials 2,153 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Thymidylate Synthase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 555 | 258 | 112 | 184 | 70% |
| Phase 2 | 1062 | 357 | 224 | 475 | 61% |
| Phase 3 | 503 | 158 | 57 | 287 | 73% |
| Phase 4 | 33 | 14 | 4 | 14 | 78% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved Thymidylate Synthase drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Thymidylate Synthase. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Thymidylate Synthase Drug Approval Timeline (2004 - 2026)
The first drug targeting TS was approved in 2004 (ALIMTA), with the most recent approval in 2026 (VYKOURA).
The approval timeline indicates a sustained interest in TS as a drug target over the past 23 years.
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
- • Sponsors: 655 (226 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 Thymidylate Synthase. A trial counts if an approved drug acting on Thymidylate Synthase 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.