Kappa-opioid receptor Agonists
10 drugsAbout Kappa-opioid receptor
The Kappa-opioid receptor (KOR) is a G protein-coupled receptor involved in pain modulation and other physiological processes. Activation of KOR leads to diverse effects, making it a target for various therapeutic areas. The gene symbol for KOR is OPRK1.
Human genetics provide moderate support for KOR as a therapeutic target, with a max genetic score of 0.50. Genetic associations include placental retention (score 0.50) and smoking initiation (score 0.50).
KOR is targeted by 10 FDA-approved small molecule drugs, including KORSUVA, SYMPROIC, and BUPRENORPHINE. These drugs are developed by 9 companies, including BDSI, ALKEM LABS LTD, and VIFOR INTL, and address pain and other therapeutic needs.
Kappa-opioid receptor Genetic Evidence Moderate
Genetic evidence offers moderate support for KOR, with a max score of 0.50.
Further research is needed to validate KOR's role in genetically-supported indications.
Evidence Across Diseases
11 totalGWAS and other genetic studies link OPRK1 to 11 diseases.
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 Kappa-opioid receptor Drugs
Nine companies have approved drugs targeting KOR, with BDSI among the top players.
The presence of multiple players suggests a competitive market with moderate entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| ZUBSOLV | EDENBRIDGE PHARMS | 2013 | 1 |
| BUTRANS | KNOA PHARMA | 2010 | 1 |
| BUPRENORPHINE | WATSON LABS TEVA | 2018 | 1 |
| SUBLOCADE | INDIVIOR | 2017 | 1 |
| VIBERZI | AbbVie | 2015 | 1 |
| BRIXADI | BRAEBURN | 2023 | 1 |
| SYMPROIC | BDSI | 2017 | 1 |
Kappa-opioid receptor Drug Modality Landscape
Modalities
Routes of Administration
Kappa-opioid receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or peptides may offer differentiation.
Kappa-opioid receptor Clinical Trials 269 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Kappa-opioid receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 58 | 46 | 5 | 7 | 90% |
| Phase 2 | 71 | 45 | 15 | 11 | 75% |
| Phase 3 | 55 | 36 | 12 | 6 | 75% |
| Phase 4 | 85 | 48 | 16 | 20 | 75% |
Top Sponsors
By Modality
Top Conditions
Kappa-opioid receptor Drug Approval Timeline (2010 - 2023)
Opioid Dependence
The first KOR-targeting drug was approved in 2010 (BUTRANS), with the most recent in 2023 (BRIXADI).
The recent approval suggests continued interest, but market saturation should be considered.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 10 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 10-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 137 (35 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 Kappa-opioid receptor. A trial counts if an approved drug acting on Kappa-opioid receptor 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.