Cereblon Inhibitors
5 drugsAbout Cereblon
Cereblon (CRBN) is a protein involved in protein homeostasis and cellular signaling. It functions as a substrate receptor for the CRL4 E3 ubiquitin ligase complex, regulating the ubiquitination of various proteins. This process impacts multiple cellular pathways, making it a compelling target for therapeutic intervention.
Human genetic studies provide strong validation for Cereblon as a therapeutic target (max score 0.94). Variants in CRBN are linked to 22 diseases, including congenital sideroblastic anemia and retinitis pigmentosa. Loss-of-function variants are associated with increased risk of autosomal recessive non-syndromic intellectual disability, suggesting activation may be beneficial.
Cereblon is targeted by 5 FDA-approved small molecule drugs, including REVLIMID, THALOMID and POMALYST, all in oncology. These drugs are marketed by Bristol-Myers Squibb, Cipla and NATCO. The first drug was approved in 1998 and the most recent in 2023.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 80% attractiveness score.
- phase1 represents biological uncertainty with 54% completion.
Cereblon Genetic Evidence Strong
Cereblon has strong genetic support with a maximum score of 0.94 linked to congenital sideroblastic anemia.
Strong genetic support suggests that clinical trials targeting Cereblon 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 1 traits
- • Strong signal in nervous system disease, genetic, familial or congenital disease, nutritional or metabolic disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link CRBN to 22 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for CRBN 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 Cereblon Drugs
Three companies, including Bristol-Myers Squibb and Cipla, have approved drugs targeting Cereblon.
The market is moderately concentrated, suggesting potential entry barriers for new competitors.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| THALOMID | Bristol-Myers Squibb | 1998 | 2 |
| THALIDOMIDE | NATCO | 2023 | 2 |
Cereblon Drug Modality Landscape
Modalities
Routes of Administration
Cereblon 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.
Cereblon Clinical Trials 1,082 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 395 | 191 | 106 | 94 | 64% |
| Phase 2 | 495 | 213 | 95 | 184 | 69% |
| Phase 3 | 174 | 62 | 14 | 98 | 82% |
| Phase 4 | 18 | 9 | 3 | 6 | 75% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved Cereblon drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Cereblon. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Cereblon Drug Approval Timeline (1998 - 2023)
The first Cereblon-targeting drug was approved in 1998, with the most recent approval in 2023.
The approval timeline indicates continued interest in Cereblon as a drug target, but also a potentially saturated market.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 3 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-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 616 clinical trials targeting Cereblon.
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