Difelikefalin
drugOn this page
Also known as CR-845CR845DifelicefalinaDifelikefalineFE-202845FE202845MR-13A9MR13A9US9359399, 2
Summary
Difelikefalin (CHEMBL3989915) is an approved protein (ATC V03AX04) targeting OPRK1; indicated across 4 conditions including osteoarthritis and chronic kidney disease.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Protein
- ATC class: V03AX04
- Targets: 1 (OPRK1)
- Indications: 4 conditions
- Clinical trials: 23
- Chemistry: 679.8 Da · C36H53N7O6
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL3989915 |
| Name | Difelikefalin |
| Type | Protein |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 24794466 |
| ATC | V03AX04 |
| Molecular formula | C36H53N7O6 |
| Molecular weight | 679.8 |
| InChIKey | FWMNVWWHGCHHJJ-SKKKGAJSSA-N |
SMILES: CC(C)C[C@H](C(=O)N[C@H](CCCCN)C(=O)N1CCC(CC1)(C(=O)O)N)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](CC3=CC=CC=C3)N
IUPAC name: 4-amino-1-[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid
Also known as: CR-845, CR845, Difelicefalina, Difelikefalin, Difelikefaline, FE-202845, FE202845, MR-13A9, MR13A9, US9359399, 2, DIFELIKEFALIN
Parent form; salt/anhydrous children: CHEMBL5315123
Patent coverage: 136 distinct patent families (315 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| OPRK1 | κ receptor | Agonist | 9.8 | 0% | P41145 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Kappa-type opioid receptor, Kappa-type opioid receptor.
Bioactivity
ChEMBL activities: 2 potent at pChembl ≥ 5 of 2 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P33534 | 10.32 | EC50 | 0.05 | nM | CHEMBL_ACT_17775581 |
| OPRK1 | 9.8 | EC50 | 0.16 | nM | CHEMBL_ACT_17775617 |
Target pathways
Aggregated over 1 target gene(s): OPRK1.
Top Reactome pathways
3 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Peptide ligand-binding receptors | 1 | OPRK1 |
| G alpha (i) signalling events | 1 | OPRK1 |
| MECP2 regulates neuronal receptors and channels | 1 | OPRK1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| immune response | 1 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| neuropeptide signaling pathway | 1 |
| chemical synaptic transmission | 1 |
| sensory perception | 1 |
| locomotory behavior | 1 |
| sensory perception of pain | 1 |
| adenylate cyclase-inhibiting opioid receptor signaling pathway | 1 |
| response to insulin | 1 |
| positive regulation of dopamine secretion | 1 |
| negative regulation of luteinizing hormone secretion | 1 |
| response to nicotine | 1 |
| G protein-coupled opioid receptor signaling pathway | 1 |
| maternal behavior | 1 |
Indications & clinical
Indications
4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| osteoarthritis | 2 | MONDO:0005178 | MONDO:0005178 |
| chronic kidney disease | 1 | MONDO:0005300 | EFO:0003884 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 23.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 9 |
| PHASE3 | 7 |
| PHASE1 | 4 |
| Not specified | 2 |
| PHASE2/PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02858726 | PHASE2/PHASE3 | COMPLETED | Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus |
| NCT03281538 | PHASE3 | COMPLETED | Extension Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus |
| NCT03422653 | PHASE3 | COMPLETED | A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1) |
| NCT03636269 | PHASE3 | COMPLETED | CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus |
| NCT03998163 | PHASE3 | COMPLETED | CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus |
| NCT04711603 | PHASE3 | COMPLETED | A Phase III Clinical Study of MR13A9 in Hemodialysis Patients With Pruritus. |
| NCT05387707 | PHASE3 | TERMINATED | Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis |
| NCT05885737 | PHASE3 | COMPLETED | Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus |
| NCT06593392 | PHASE2 | RECRUITING | Safety and Tolerability of Difelikefalin in Adolescents on Haemodialysis With Moderate-to-Severe Pruritus |
| NCT00877799 | PHASE2 | COMPLETED | Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery |
| NCT01361568 | PHASE2 | COMPLETED | Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery |
| NCT01789476 | PHASE2 | COMPLETED | A Phase 2 Study to Evaluate Analgesic Effect of IV CR845 For Pain Following Bunionectomy Surgery |
| NCT02524197 | PHASE2 | COMPLETED | A Study of the Safety and Effectiveness of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee |
| NCT03802617 | PHASE2 | COMPLETED | A Clinical Study of MR13A9 in Hemodialysis Patients With Pruritus. |
| NCT03995212 | PHASE2 | TERMINATED | Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus |
| NCT04018027 | PHASE2 | COMPLETED | Study to Evaluate the Efficacy and Safety of Oral Difelikefalin (CR845) for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis |
| NCT04706975 | PHASE2 | COMPLETED | Study to Evaluate the Efficacy and Safety of Oral Difelikefalin (CR845) for Moderate to Severe Pruritus in Subjects With Notalgia Paresthetica (KOMFORT) |
| NCT03947970 | PHASE1 | COMPLETED | Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 (Difelikefalin) in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects |
| NCT04019574 | PHASE1 | COMPLETED | Study to Investigate the Effects of Single Intravenous Doses of Difelikefalin (CR845) on the QTc Interval in Healthy Subjects |
| NCT05533008 | PHASE1 | COMPLETED | CR845-100303: Study to Assess the Potential of Physical Withdrawal From Intravenous CR845 (Difelikefalin) in Hemodialysis Patients |
| NCT05885763 | PHASE1 | COMPLETED | Pharmacokinetics of Intravenous Difelikefalin in Chinese Adult Subjects on Haemodialysis |
| NCT07526324 | Not specified | NOT_YET_RECRUITING | Difelikefalin for Itching in Hemodialysis Patients With Chronic Kidney Disease |
| NCT05031546 | Not specified | APPROVED_FOR_MARKETING | Intermediate-Size Patient Population Expanded Access Program for Intravenous Difelikefalin |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
347 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | OPRK1 |
| ALOGLIPTIN | ChEMBL + PubChem | Phase 4 (approved) | OPRK1 |
| PROPOXYPHENE | ChEMBL + PubChem | Phase 4 (approved) | OPRK1 |
| ACRIVASTINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ALMITRINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ALPIDEM | ChEMBL | Phase 4 (approved) | OPRK1 |
| ALPRAZOLAM | ChEMBL | Phase 4 (approved) | OPRK1 |
| ALVIMOPAN | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ATAZANAVIR | ChEMBL | Phase 4 (approved) | OPRK1 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | OPRK1 |
| AZATADINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BACAMPICILLIN | ChEMBL | Phase 4 (approved) | OPRK1 |
| BECLOBRATE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| BENZNIDAZOLE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BENZPHETAMINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | OPRK1 |
| BIFONAZOLE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BISACODYL | ChEMBL | Phase 4 (approved) | OPRK1 |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | OPRK1 |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUCLIZINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUFLOMEDIL | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUPRENORPHINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUPROPION | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUTOCONAZOLE | ChEMBL | Phase 4 (approved) | OPRK1 |
| BUTORPHANOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CANRENONE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CARTEOLOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CHLOPHEDIANOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CHLORDIAZEPOXIDE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CHLOROXINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CICLESONIDE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CILOSTAZOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CINACALCET | ChEMBL | Phase 4 (approved) | OPRK1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CLIOQUINOL | ChEMBL | Phase 4 (approved) | OPRK1 |
| CLOBAZAM | ChEMBL | Phase 4 (approved) | OPRK1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | OPRK1 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | OPRK1 |
Related Atlas pages
- Genes: OPRK1
- Drugs: Aclidinium Bromide, Alogliptin, Propoxyphene, Acrivastine, Almitrine, Alpidem, Alprazolam, Alvimopan, Ambenonium, Amiodarone, Amitriptyline, Amlodipine, Amoxapine, Amsacrine, Apomorphine, Aripiprazole, Astemizole, Atazanavir, Atomoxetine, Atracurium, Azatadine, Bacampicillin, Beclobrate, Benperidol, Benznidazole, Benzphetamine, Benztropine, Bepridil, Bifonazole, Bisacodyl, Bosutinib, Bromocriptine, Bromperidol, Buclizine, Buflomedil, Buprenorphine, Bupropion, Butoconazole, Butorphanol, Calcitriol, Candesartan Cilexetil, Cannabidiol, Canrenone, Carteolol, Carvedilol, Chlophedianol, Chlordiazepoxide, Chlorhexidine, Chloroxine, Chlorpromazine, Ciclesonide, Cilostazol, Cinacalcet, Cinnarizine, Cisapride, Clemastine, Clioquinol, Clobazam, Clofazimine, Clomipramine