Protein / target

Kappa-type opioid receptor

OPRK1P41145Homo sapiensSwiss-Prot
UniProt: P41145Ensembl: ENSG00000082556HGNC: HGNC:8154NCBI Gene: 4986
Clinically validated
Therapeutic maturity
31
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

G protein-coupled opioid receptor activity

Primary system

Nervous system

Strongest disease association

alcohol dependence

Clinical evidence · score 0.62

Therapeutic maturity

Clinically validated target

31 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

31 approved · 7 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

G protein-coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Subcellular location

Cell membrane
Domains and Gene Ontology detail (46)

Gene Ontology

  • Caxon terminus
  • Cdendrite
  • Cmembrane
  • Cmitochondrion
  • Cneuron projection
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic membrane
  • Cpresynaptic membrane
  • Csarcoplasmic reticulum
  • Csynaptic vesicle membrane
  • CT-tubule

380 aa · 43 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingUniProt · GOSynaptic signallingGOIon channel gatingGOImmune signallingGOMotor controlGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled opioid receptor that functions as a receptor for endogenous alpha-neoe…
  • ·G protein-coupled opioid receptor activity
  • ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • ·G protein-coupled opioid receptor signaling pathway

Synaptic signalling

  • ·postsynaptic membrane
  • ·presynaptic membrane
  • ·chemical synaptic transmission

Ion channel gating

  • ·positive regulation of potassium ion transmembrane transport

Immune signalling

  • ·immune response

Motor control

  • ·locomotory behavior
View underlying pathways (3)
Peptide ligand-binding receptors
G alpha (i) signalling events
MECP2 regulates neuronal receptors and channels

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Buprenorphine
Narrow target profileApprovedAgonist

Kappa opioid receptor agonist

Appears in clinical studies involving drug dependence, opiate dependence, overdose, Chronic pain

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

Naltrexone
ApprovedAntagonist

Opioid receptors; mu/kappa/delta antagonist

Appears in clinical studies involving alcohol dependence, Overweight, Obesity, Borderline personality disorder

Acts on a complex — shared with OPRD1, OPRM1 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

Pain1.00

Clinical · overall 0.61

opiate dependence0.99

Clinical · overall 0.61

alcohol dependence0.99

Clinical · overall 0.62

migraine disorder0.97

Clinical · overall 0.60

drug dependence0.97

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Pruritus0.59

Clinical

major depressive disorder0.58

Clinical

Chronic pain0.58

Clinical

osteoarthritis0.57

Clinical

Obesity0.57

Clinical

Show all associations
alcohol dependence0.62
Pain0.61
opiate dependence0.61
migraine disorder0.60
drug dependence0.60
Pruritus0.59
major depressive disorder0.58
Chronic pain0.58
osteoarthritis0.57
Obesity0.57

Open Targets ranks 425 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 38 total

DIFELIKEFALINApproval

Pruritus · chronic kidney disease · atopic eczema

DEZOCINEApproval

Pain · polyp of large intestine · laryngeal carcinoma

HYDROCODONE BITARTRATEApproval

Pain · drug dependence · Chronic pain

DEXTROMORAMIDEApproval

Pain

ANILERIDINE HYDROCHLORIDEApproval

Pain

SAMIDORPHAN L-MALATEApproval

schizophrenia · bipolar I disorder

NALOXONEApproval

Constipation · opiate dependence · major depressive disorder

HYDROCODONEApproval

Pain · Cough · Chronic pain

BUTORPHANOLApproval

Pain

NALTREXONE HYDROCHLORIDEApproval

Pain · Self-injurious behavior · Intellectual disability

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Safety liabilities

dizzinesstachycardiadizzinessinteraction with dopaminergic transmission and hallucinationdecreased/increased heart rateincreased convulsionsincreased/decreased eatingdecreased body temperaturedecreased eatingdiuresispsychotomimetic effectsdecreased convulsions

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Gradual Vs. Rapid Buprenorphine DetoxificationPHASE1

COMPLETED · via Buprenorphine · NCT00000220

Buprenorphine Maintenance Treatment of Opioid Dependence in Primary Care: A Randomized Clinical Trial of At-Home Versus In-Office Buprenorphine InductionPHASE2/PHASE3

COMPLETED · via Buprenorphine · NCT00684554

Pharmacogenetic Investigation of NaltrexonePHASE2

COMPLETED · via Naltrexone · NCT00270231

Buprenorphine Detoxification With Two Types of Treatment. BBD IIIPHASE2

COMPLETED · via Buprenorphine · NCT00000230

Low Dose Naltrexone (LDN) Immune MonitoringNA

COMPLETED · via Naltrexone · NCT02107014

HIV Risk Reduction and Drug Abuse Treatment in IranPHASE2

WITHDRAWN · via Naltrexone · NCT00398008

Show remaining trials (24)
Low Dose Naltrexone (LDN) for the Treatment of Chronic Neuropathic Pain in Patients With Human Immunodeficiency Virus (HIV), a Prospective, Pragmatic, Open Label Clinical TrialPHASE4

RECRUITING · via Naltrexone · NCT05537935

Dopamine D2/3- and μ-opioid Receptor Antagonists Reduce Cue-induced Reward Responding and Reward Impulsivity in Healthy VolunteersNA

COMPLETED · via Naltrexone · NCT02557984

Adherence to HIV Therapy in Heroin Addicts: Oral vs. Extended Release NaltrexonePHASE2

COMPLETED · via Naltrexone · NCT01101815

Buprenorphine Pharmacology Related to Addiction TreatmentPHASE2

COMPLETED · via Buprenorphine · NCT00000239

A Randomized, Double-Blinded Clinical Trial to Evaluate the Effectiveness of Naltrexone in Improving Nonsuicidal Self-Injurious BehaviorNA

NOT_YET_RECRUITING · via Naltrexone · NCT07641283

Optimal Treatment of Veterans With PTSD and Comorbid Opiate Use Disorder (OUD)PHASE2

TERMINATED · via Buprenorphine · NCT03605342

Naltrexone and Nicotine Replacement Effects on Cue Reactivity of SmokersNA

COMPLETED · via Naltrexone · NCT00018213

The Evaluation of Safety and Tolerance of Commercially Available Naltrexone Administered Daily - Assessment for CBRN OperationsPHASE1

COMPLETED · via Naltrexone · NCT03879460

Extended-release Pharmacotherapy for Opioid Use Disorder (EXPO): Protocol for an Open-label Randomised Controlled Trial of Injectable Maintenance Buprenorphine With Personalised Psychosocial Intervention.PHASE3

COMPLETED · via Buprenorphine · NCT05164549

Alternate-Day Buprenorphine Administration. Phase VIIIPHASE2

COMPLETED · via Buprenorphine · NCT00000227

A Double-Blind, Double-Dummy, Placebo- and Active Controlled Evaluation of the Efficacy, Safety and Tolerability of Buprenorphine HCl Buccal Film in the Treatment of Pain Associated With Third Molar ExtractionPHASE2

COMPLETED · via Buprenorphine · NCT00941304

Intravenous Buprenorphine Versus Morphine for Severe Pain in the Emergency DepartmentPHASE2

UNKNOWN · via Buprenorphine · NCT03256487

Behavioral/Pharmacological Treatments for Alcohol-Nicotine DependencePHASE4

COMPLETED · via Naltrexone · NCT00000447

Pharmacological Comparison of Buprenorphine and MethadonePHASE2

COMPLETED · via Buprenorphine · NCT00000334

Neuropharmacological Basis of Social Connection: The Role of OpioidsNA

COMPLETED · via Naltrexone · NCT01672723

The Use of Naltrexone Hydrochloride to Promote Healing in Patients With Resistant Non-infectious Corneal UlcerNA

COMPLETED · via Naltrexone · NCT05924893

A Multicenter, Randomized, Double-blind, Active Comparator Study to Determine the Efficacy and Safety of BTDS 20 or Oxycodone Immediate-release Versus BTDS 5 in Subjects With Moderate to Severe Low Back PainPHASE3

TERMINATED · via Buprenorphine · NCT00313014

A Prospective, Randomized Trial of the Effect of Buprenorphine Continuation Versus Dose Reduction on Pain Control and Post-Operative Opioid UsePHASE4

TERMINATED · via Buprenorphine · NCT04981678

Randomized, Double-blind, Placebo-controlled Study of Naltrexone for Impulse Control Disorders in Parkinson's DiseasePHASE4

COMPLETED · via Naltrexone · NCT01052831

Incomplete Response in Late-Life Depression: Getting to Remission With BuprenorphinePHASE1/PHASE2

COMPLETED · via Buprenorphine · NCT02263248

Combined Treatment for Cocaine-Alcohol DependencePHASE2

COMPLETED · via Naltrexone · NCT00218569

Naltrexone for At-Risk and Problem Drinking in Smoking Cessation TreatmentPHASE2

COMPLETED · via Naltrexone · NCT00938886

Behavioral Naltrexone Therapy (BNT) for Promoting Adherence to Oral Naltrexone (BNT-oral) vs Extended Release Injectable Depot Naltrexone (Depot-BNT); a Randomized TrialPHASE3

COMPLETED · via Naltrexone · NCT00577408

Opiate Dependence: Combined Naltrexone/Behavior TherapyPHASE2

COMPLETED · via Naltrexone · NCT00238914

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

alcohol dependenceWell supported
0.76
agreement 0.61–0.92
Clinical91%Literature9%

Open Targets aggregate 0.62 · 2 independent evidence families

PainWell supported
0.75
agreement 0.60–0.91
Clinical99%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

opiate dependenceModerately supported
0.75
agreement 0.59–0.90
Clinical97%Literature3%

Open Targets aggregate 0.61 · 2 independent evidence families

migraine disorderModerately supported
0.74
agreement 0.58–0.89
Clinical96%Literature4%

Open Targets aggregate 0.60 · 2 independent evidence families

drug dependenceModerately supported
0.73
agreement 0.58–0.89
Clinical98%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

60

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-07-13

    Label change: BUPRENORPHINE (ANDA204937)

    fda · regulatory · fda · via Buprenorphine

  2. Label change2026-07-13

    Label change: BUPRENORPHINE (ANDA204937)

    fda · regulatory · fda · via Buprenorphine

  3. Label change2026-07-13

    Label change: BUPRENORPHINE (ANDA204937)

    fda · regulatory · fda · via Buprenorphine

  4. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (ANDA207490)

    fda · regulatory · fda · via Buprenorphine

  5. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (ANDA210272)

    fda · regulatory · fda · via Buprenorphine

  6. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (ANDA211586)

    fda · regulatory · fda · via Buprenorphine

  7. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (ANDA204937)

    fda · regulatory · fda · via Buprenorphine

  8. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (ANDA210162)

    fda · regulatory · fda · via Buprenorphine

  9. Supplemental approval2026-06-18

    Supplemental approval: BUPRENORPHINE (NDA021306)

    fda · regulatory · fda · via Buprenorphine

  10. Label change2025-12-22

    Label change: BUPRENORPHINE (NDA021306)

    fda · regulatory · fda · via Buprenorphine

  11. Withdrawn from market2025-06-19

    Market withdrawal: Sixmo (EMA)

    ema · market · ema · via Buprenorphine

  12. Label change2025-03-14

    Label change: BUPRENORPHINE (ANDA210162)

    fda · regulatory · fda · via Buprenorphine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.