Topoisomerase I Inhibitors
4 drugsAbout Topoisomerase I
Topoisomerase I (TOP1) is an enzyme that relieves torsional stress during DNA replication and transcription by cutting and rejoining single DNA strands. Inhibiting TOP1 disrupts DNA metabolism, especially in rapidly dividing cells, making it a target for oncology drugs.
Human genetics provide moderate support for TOP1 as a therapeutic target, with variants linked to hypercholesterolemia (score 0.67) and autism spectrum disorder (score 0.55). Strong eQTL/pQTL signals further support TOP1's role in disease.
Six FDA-approved drugs target TOP1, including ENHERTU, IRINOTECAN HYDROCHLORIDE, and DATROWAY. These drugs are split between small molecules and ADCs, with applications in oncology and other therapeutic areas.
Topoisomerase I Genetic Evidence Moderate
Genetic evidence shows moderate support for Topoisomerase I as a drug target.
Further research into the genes regulated by TOP1 could reveal novel therapeutic opportunities.
Evidence Across Diseases
14 totalGWAS and other genetic studies link TOP1 to 14 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for TOP1 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 Topoisomerase I Drugs
Six companies have approved drugs targeting Topoisomerase I, including QILU PHARM HAINAN and DAIICHI SANKYO.
The presence of multiple players suggests a competitive market, requiring a strong value proposition for new entrants.
Topoisomerase I Drug Modality Landscape
Modalities
Routes of Administration
Topoisomerase I is amenable to small molecule drugs, with oral options available for convenient dosing.
Consider novel modalities to differentiate from existing Topoisomerase I-targeting therapies.
Topoisomerase I Clinical Trials 651 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Topoisomerase I. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 244 | 124 | 43 | 75 | 74% |
| Phase 2 | 276 | 122 | 65 | 88 | 65% |
| Phase 3 | 124 | 37 | 9 | 78 | 80% |
| Phase 4 | 7 | 1 | 0 | 5 | 100% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved Topoisomerase I drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Topoisomerase I. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Topoisomerase I Drug Approval Timeline (1996 - 2015)
The first Topoisomerase I-targeting drug was approved in 1996, with the most recent in 2025.
The continued approval of new drugs indicates sustained interest in Topoisomerase I as a target.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 297 (102 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 Topoisomerase I. A trial counts if an approved drug acting on Topoisomerase I 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.