Ribonucleotide reductase Inhibitors
8 drugsAbout Ribonucleotide reductase
Ribonucleotide reductase (RNR) catalyzes deoxyribonucleotide formation, essential for DNA synthesis and cell proliferation. As a critical enzyme for DNA production, RNR is a target for drugs aimed at rapidly dividing cells.
Genetic studies offer moderate support for RRM1 (max score 0.66), with variants linked to progressive external ophthalmoplegia. This suggests that modulating RNR activity could be therapeutically beneficial in proliferative diseases.
RNR is targeted by 8 approved small molecule drugs, including AVGEMSI, INLEXZO, and HYDREA, across oncology, rare diseases, and other therapeutic areas. First approved in 1967, the most recent approval was in 2025.
Ribonucleotide reductase Genetic Evidence Moderate
Genetic evidence shows moderate support (max score 0.66) linking RRM1 to progressive external ophthalmoplegia.
Further research into the genetic associations of RRM1 could reveal novel therapeutic opportunities.
Evidence Across Diseases
6 totalGWAS and other genetic studies link RRM1 to 6 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for RRM1 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 Ribonucleotide reductase Drugs
Eight companies have approved drugs targeting RNR, including Hikma, TEYRO LABS and AVYXA HOLDINGS.
The presence of multiple players suggests a competitive market, requiring a differentiated approach for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| AVGEMSI | AVYXA HOLDINGS | 2025 | 4 |
| INLEXZO | Johnson & Johnson | 2025 | 2 |
| CLOFARABINE | MLV | 2017 | 1 |
| XROMI | NOVA LABS LTD | 2024 | 1 |
| SIKLOS | THERAVIA | 2017 | 1 |
Ribonucleotide reductase Drug Modality Landscape
Modalities
Routes of Administration
Ribonucleotide reductase is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or PROTACs could provide a competitive advantage.
Ribonucleotide reductase Clinical Trials 2,255 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Ribonucleotide reductase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 1009 | 370 | 246 | 375 | 60% |
| Phase 2 | 937 | 376 | 227 | 330 | 62% |
| Phase 3 | 292 | 103 | 40 | 148 | 72% |
| Phase 4 | 17 | 8 | 4 | 5 | 67% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
2 Phase 3 trials testing approved Ribonucleotide reductase drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Ribonucleotide reductase. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Ribonucleotide reductase Drug Approval Timeline (1967 - 2025)
The first RNR-targeting drug was approved in 1967, with the most recent in 2025, spanning 59 years.
The continued approval of RNR-targeting drugs indicates sustained interest and potential for further innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 682 (244 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 Ribonucleotide reductase. A trial counts if an approved drug acting on Ribonucleotide reductase 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.