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.
Strategic Insights
ℹ️ How we calculate- phase1 represents biological uncertainty with 52% completion.
Human 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 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 |
|---|---|---|---|
| HYDREA | WAYLIS THERAP | 1967 | 2 |
| FLUDARABINE PHOSPHATE | Fresenius Kabi | 2003 | 1 |
| CLOFARABINE | PHARMOBEDIENT | 2017 | 1 |
| XROMI | NOVA LABS LTD | 2024 | 1 |
| SIKLOS | THERAVIA | 2017 | 1 |
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.
Clinical Trials 2,641 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 1107 | 436 | 256 | 402 | 63% |
| Phase 2 | 1148 | 454 | 264 | 423 | 63% |
| Phase 3 | 365 | 122 | 47 | 195 | 72% |
| Phase 4 | 21 | 10 | 5 | 6 | 67% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
3 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.
Drug Approval Timeline (1967 - 2025)
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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
- • Competition: High (15 sponsors)
- • 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 1738 clinical trials targeting Ribonucleotide reductase.
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