CDK4 Inhibitors
4 drugsAbout CDK4
Cyclin Dependent Kinase 4 (CDK4) is a protein kinase regulating cell cycle progression from G1 to S phase. It forms complexes with D-type cyclins to phosphorylate and inactivate the retinoblastoma protein (Rb), promoting cell proliferation.
Human genetics provide strong validation of CDK4 as a therapeutic target, with variants linked to cutaneous melanoma (score 0.84) and familial melanoma (score 0.80). Inhibition is likely beneficial based on genetic evidence.
CDK4 is targeted by 4 FDA-approved small molecule drugs including IBRANCE, KISQALI, VERZENIO and COSELA, with applications in oncology and other therapeutic areas.
Strategic Insights
ℹ️ How we calculate- Validated target with strong trial activity and 80% attractiveness score.
- phase3 represents biological uncertainty with 50% completion.
Human Genetic Evidence Strong
CDK4 has strong genetic support with a max score of 0.84 linking it to cutaneous melanoma.
Strong genetic support suggests that clinical trials targeting CDK4 in melanoma have a higher probability of success.
💡 Why inhibition?
- • Gain-of-function variants increase disease risk — blocking overactivity may help
- • 100% directional consistency across 1 traits
- • Strong signal in integumentary system disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
7 totalGWAS and other genetic studies link CDK4 to 7 diseases.
Gain-of-function causes disease; inhibition may help
🔗 Colocalization Evidence 4 strong
max H4: 1.00eQTL/pQTL signals for CDK4 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
The competitive landscape includes four companies with approved drugs: Pfizer, Novartis, Eli Lilly, and PHARMACOSMOS.
The presence of multiple players indicates moderate competition, but also potential for partnerships or acquisitions.
Drug Modality Landscape
Modalities
Routes of Administration
CDK4 is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities like antibodies or fusion proteins represents a whitespace opportunity for innovation.
Clinical Trials 561 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 224 | 95 | 34 | 93 | 74% |
| Phase 2 | 242 | 81 | 31 | 128 | 72% |
| Phase 3 | 73 | 18 | 10 | 45 | 64% |
| Phase 4 | 22 | 9 | 7 | 6 | 56% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved CDK4 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting CDK4. 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 (2015 - 2021)
The approval timeline for CDK4 inhibitors spans 7 years, with the first drug approved in 2015 and the most recent in 2021.
The relatively short approval span suggests continued interest and potential for further drug development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 companies competing
- • Market share by company
Full Drug Portfolio
- • All 4 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 4-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 507 clinical trials targeting CDK4.
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