LCK Inhibitors
7 drugsAbout LCK
LCK (lymphocyte-specific protein tyrosine kinase) is a non-receptor tyrosine kinase crucial for T-cell receptor signaling and T cell development. It initiates downstream signaling cascades, leading to T cell activation and immune responses.
Human genetics provide strong validation for LCK as a therapeutic target, with variants linked to severe combined immunodeficiency (score 0.81). Loss-of-function variants increase disease risk, suggesting activation of LCK may be beneficial.
LCK is targeted by 7 FDA-approved small molecule drugs, including Sprycel, Phyrago and Pazopanib Hydrochloride. These drugs are primarily used in oncology (5 drugs) and respiratory diseases (1 drug).
LCK Genetic Evidence Strong
Genetic evidence strongly supports LCK's role in severe combined immunodeficiency (score 0.81).
Strong genetic support increases the likelihood of clinical success for LCK-targeting therapies.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 2 traits
- • Strong signal in immune system disease, genetic, familial or congenital disease, phenotype pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
2 totalGWAS and other genetic studies link LCK to 2 diseases.
Loss-of-function causes disease; activation may help
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 LCK Drugs
Seven companies have approved drugs targeting LCK, including NOVUGEN, Apotex, and Bristol-Myers Squibb.
The presence of multiple players indicates a competitive market, requiring a differentiated therapeutic approach.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| DASATINIB | Teva | 2016 | 2 |
| PAZOPANIB HYDROCHLORIDE | EUGIA PHARMA | 2023 | 2 |
| PHYRAGO | HANDA THERAP | 2023 | 2 |
| VIZIMPRO | Pfizer | 2018 | 1 |
LCK Drug Modality Landscape
Modalities
Routes of Administration
LCK 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.
LCK Clinical Trials 479 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on LCK. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 181 | 111 | 47 | 23 | 70% |
| Phase 2 | 239 | 129 | 60 | 49 | 68% |
| Phase 3 | 41 | 26 | 3 | 12 | 90% |
| Phase 4 | 18 | 12 | 1 | 5 | 92% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
LCK Drug Approval Timeline (2006 - 2023)
The first LCK-targeting drug was approved in 2006 (Sprycel), with the most recent approval in 2023 (Phyrago).
The continued approval of LCK-targeting drugs suggests ongoing opportunities for innovation in this space.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 216 (33 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 LCK. A trial counts if an approved drug acting on LCK 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.