Difelikefalin
Difelikefalin is an FDA-approved peripheral kappa opioid receptor agonist. Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists.
For research use only.
Key Facts
- CAS
- 1024828-77-0
- Molecular Weight (MW)
- 679.8 g/mol
- Half-life
- —
- FDA status
- Approved
- Administration Route
- intravenous
- Frequency
- —
- Last updated
- Aug 30, 2026
- Reviewed
- Aug 30, 2026
Research summary
Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis.
Peptide Library's Difelikefalin profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
Protocol
- Dosage Range
- —
- Frequency
- —
- Cycle
- —
- Administration Route
- intravenous
- Reconstitution Guide
- —
Not yet checked against primary sources
These figures are compiled from earlier reference material. They have not been verified against FDA labelling, registered trials or published literature, no citation is attached to them, and none of them is a recommended dose. Difelikefalin is queued for dosage evidence review.
Compare reported doses across the whole librarySequence & molecular data
| Molecular formula | C36H53N7O6 |
|---|---|
| Molecular weight | 679.8 g/mol |
| CAS number | 1024828-77-0 |
| PubChem CID | 24794466 |
| FDA UNII | NA1U919MRO |
| ChEMBL | CHEMBL3989915 |
| DrugBank | DB11938 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists.
Studies
- A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus
- Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis
- Intravenous difelikefalin for the treatment of hemodialysis pruritus
- Pharmacological interventions for pruritus in adult palliative care patients
- Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis
Regulatory & research status
Difelikefalin is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.
| FDA status | Approved |
|---|---|
| Research status | Approved product (see FDA status) |
| Availability | Prescription-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | FDA-Approved |
Benefits
—
Potential Side Effects
No side effects listed yet for this entry.
Storage & stability
Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.
Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.
Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.
Read the full guide: how to store peptides before and after reconstitution →
Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.
Difelikefalin: frequently asked questions
What is Difelikefalin?
Peripherally restricted kappa opioid receptor agonist approved for moderate-to-severe pruritus associated with chronic kidney disease in adults on haemodialysis.
How does Difelikefalin work?
Difelikefalin is a synthetic D-amino-acid tetrapeptide whose hydrophilicity and charge prevent meaningful penetration of the central nervous system. It activates kappa opioid receptors on peripheral sensory neurons and immune cells, reducing itch signalling and inflammatory mediator release without the dysphoria, sedation, and abuse potential associated with centrally acting kappa agonists.
Is Difelikefalin FDA approved?
Yes. Difelikefalin is approved by the FDA, and approved products are prescription medicines. Approval is always for specific indications studied in clinical trials, so an approved status does not mean the compound is approved for every use it is discussed for. Research-chemical material sold under the same name is not the approved product.
What peptides are similar to Difelikefalin?
Compounds most often compared with Difelikefalin include Angiotensin II, Cetrorelix, Corticorelin and Cosyntropin. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus — N Engl J Med, 2020External reference
- Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis — J Ren Care, 2025External reference
- Intravenous difelikefalin for the treatment of hemodialysis pruritus — Expert Rev Clin Immunol, 2024External reference
- Pharmacological interventions for pruritus in adult palliative care patients — Cochrane Database Syst Rev, 2023External reference
- Difelikefalin for the treatment of moderate-to-severe pruritus associated with chronic kidney disease on hemodialysis — Expert Rev Clin Pharmacol, 2023External reference
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Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Aug 30, 2026 · Version 1
This Difelikefalin profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
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