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.
Human 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 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 |
|---|---|---|---|
| POMALYST | Bristol-Myers Squibb | 2013 | 2 |
| THALIDOMIDE | NATCO | 2023 | 2 |
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.
Clinical Trials 1,090 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 404 | 200 | 105 | 95 | 66% |
| Phase 2 | 493 | 209 | 95 | 185 | 69% |
| Phase 3 | 173 | 63 | 14 | 96 | 82% |
| Phase 4 | 20 | 10 | 3 | 7 | 77% |
Top Sponsors
By Modality
Top Conditions
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.
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