OPRK1 opioid receptor kappa 1
ENSG00000082556 · protein coding · Open Targets profile
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. {ECO:0000269|PubMed:12004055, ECO:0000269|PubMed:22437504, ECO:0000269|PubMed:7624359, ECO:0000269|PubMed:8060324}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.611549973487854 (upper bound 0.9416700005531311). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against OPRK1 (difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrate), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Adam BisagaNew York State Psychiatric Institute · 2 of 3 trials Phase 2+
- Erol OnelCali Biosciences · 2 of 2 trials Phase 2+
- Frederick G MoellerVirginia Commonwealth University · 2 of 2 trials Phase 2+
- James R LangabeerThe University of Texas Health Science Center, Houston · 2 of 2 trials Phase 2+
- Kathryn HawkYale University · 2 of 2 trials Phase 2+
- Luana CollocaUniversity of Maryland Baltimore School of Nursing · 2 of 2 trials Phase 2+
- Meredith HawkinsAlbert Einstein College of Medicine · 2 of 2 trials Phase 2+
- Patrick BachCentral Institute of Mental Health, Mannheim · 2 of 2 trials Phase 2+
- Stefanie MorganAgelessRx · 2 of 2 trials Phase 2+
- Suxia LuoHenan Cancer Hospital · 2 of 2 trials Phase 2+
- Toufic R JildehResident · 2 of 2 trials Phase 2+
- Caitlin E SmithMedical University of South Carolina · 1 of 2 trials Phase 2+
- Jessica MoeUniversity of British Columbia · 1 of 2 trials Phase 2+
- Milica EnoiuVifor Pharma Group · 1 of 2 trials Phase 2+
- Mostafa BorahayJohns Hopkins University · 1 of 2 trials Phase 2+
Registry trials of difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrate updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 370 of 379 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 21 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
190 trials of drugs against OPRK1 were stopped early; 20 give no reason
Terminated, withdrawn and suspended interventional trials of difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrate, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 190.
- withdrawn · 2026-09-17 · Sahlgrenska University Hospital · matched by the registry's drug synonyms“Slow inclusion rate. Awaiting results from NCT02132416.”
- terminated · 2026-07-29 · Leiden University Medical Center · Naloxone Hydrochloride“Recruitment of chronic opioid users was substantially lower than anticipated despite extensive recruitment efforts; the study was therefore closed before reaching the planned sample size.”
- terminated · 2026-07-10 · Stanford University · matched by the registry's drug synonyms“Study terminated due to early participant drop out”
- terminated · 2026-06-15 · Wake Forest University Health Sciences · matched by the registry's drug synonyms“Study initially suspended following an audit and need of amendment to address deficiencies. PI requested to terminate due to lack of support.”
- terminated · 2026-06-04 · University of California, Irvine · Remifentanil +ultra-low dose naloxone“Study terminated early due to low enrollment. Only 8 participants enrolled out of the target 105.”
- terminated · 2026-06-02 · National Institute on Drug Abuse (NIDA) · matched by the registry's drug synonyms“Drug availability”
- terminated · 2026-05-19 · Albert Einstein College of Medicine · naloxone“Protocol was terminated due to enrollment + feasibility issues. Aim 2 not conducted. Aims 1 + 3 were conducted in part. During Aim 3 the IRB requested that the study be transitioned under a new protocol (2018-9208) in order to simplify reporting.”
- terminated · 2026-05-08 · Theresa Jacob, PhD, MPH · Buprenorphine/Naloxone“Principal Investigator is no longer at this site”
- terminated · 2026-05-08 · Montefiore Medical Center · matched by the registry's drug synonyms“Difficulty recruiting and enrolling participants”
- terminated · 2026-04-07 · University of Pennsylvania · Buprenorphine/naloxone“Funding not renewed”
- withdrawn · 2026-04-02 · New York State Psychiatric Institute · matched by the registry's drug synonyms“The U.S. Department of Health and Human Services Office of Human Research Protections issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023.”
- withdrawn · 2026-03-09 · Universidad Europea de Canarias · matched by the registry's drug synonyms“Study not initiated prior to enrollment.”
- terminated · 2026-02-10 · Baylor College of Medicine · matched by the registry's drug synonyms“After reviewing our enrollment numbers and feasibility, we have decided to close the study due to low enrollment.”
- suspended · 2026-02-03 · Friends Research Institute, Inc. · Buprenorphine/Naloxone“Unable to recruit from study sites.”
- withdrawn · 2026-01-15 · Massachusetts General Hospital · Buprenorphine/Naloxone“lack of funding”
- withdrawn · 2025-12-31 · Massachusetts General Hospital · Buprenorphine/naloxone“lack of funding”
- withdrawn · 2025-12-23 · Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) · matched by the registry's drug synonyms“No participants met eligibility and the study was closed.”
- terminated · 2025-09-16 · The University of Texas Health Science Center, Houston · matched by the registry's drug synonyms“Unable to recruit eligible participants and expiration of study medication.”
- terminated · 2025-09-11 · Albert Einstein College of Medicine · Naloxone, Placebo (for Naloxone)“Study suspended for a prolonged duration due to the Pandemic. Once research resumed project was streamlined due to insufficient resources. Study was sufficiently powered to conduct analysis for 2 of the arms. Remaining Aims were never initiated.”
- terminated · 2025-08-19 · Rosemary Claire Roden · matched by the registry's drug synonyms“Low enrollment numbers, pharmacy not able to acquire sufficient study article component (methylcellulose) due to manufacturer backorder”
- terminated · 2025-08-03 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“<75% participation”
- withdrawn · 2025-06-03 · University of Miami · matched by the registry's drug synonyms“Study drug was not compliant with research pharmacy”
- terminated · 2025-03-26 · University of California, San Francisco · Naloxone Hydrochloride“The COVID-19 Pandemic prevented us from meeting target goals.”
- terminated · 2025-03-26 · AstraZeneca · Buprenorphine / Naloxone“Study terminated due to discontinuation of the AZD4041 clinical development program for OUD.”
- terminated · 2025-03-19 · University of California, San Francisco · matched by the registry's drug synonyms“Study stopped because sufficient pilot data collected to proceed to next clinical trial.”
Paediatric incentives and obligations for OPRK1's drugs
For difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrate: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · OPRK1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000237641 (Difelikefalin, Treatment of chronic kidney disease associated pruritus): PM: decision on the application for modification of an agreed PIP, 16 May 2025; EMEA-001567-PIP01-13-M03 (naloxone (hydrochloride), Treatment of opioid-induced constipation): PM: decision on the application for modification of an agreed PIP, 7 May 2018; EMEA-001762-PIP01-15 (hydromorphone (hydrochloride);naloxone (hydrochloride), Treatment of opioid-induced constipation;Treatment of pain): W: decision granting a waiver in all age groups for all conditions or indications, 2 Oct 2015; EMEA-001713-PIP02-14 (Ibuprofen;codeine, Treatment of pain): W: decision granting a waiver in all age groups for all conditions or indications, 1 Apr 2015; +4 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrateRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Suboxone: withdrawn since 26 Sept 2006; Kapruvia: authorised since 25 Apr 2022; Zubsolv: authorised since 10 Nov 2017; Selincro: authorised since 24 Feb 2013; +1 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrateRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 130 interventional studies of difelikefalin, hydrocodone bitartrate, dextromoramide, anileridine, samidorphan l-malate, ondelopran, codeine, benzhydrocodone, levallorphan, naloxone, nalfurafine, nalmefene hydrochloride dihydrate include patients under 18; 22 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 37 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.