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.
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 |
|---|---|---|---|
| LENALIDOMIDE | ALVOGEN | 2021 | 4 |
| 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 1,127 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Cereblon. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 401 | 195 | 106 | 98 | 65% |
| Phase 2 | 515 | 217 | 97 | 201 | 69% |
| Phase 3 | 190 | 65 | 15 | 110 | 81% |
| Phase 4 | 21 | 10 | 3 | 8 | 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.
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
- • Sponsors: 361 (79 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 Cereblon. A trial counts if an approved drug acting on Cereblon 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.