Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C36H53N7O6 |
| Molecular Weight | 679.8493 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@@H](NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](N)CC2=CC=CC=C2)C(=O)N[C@H](CCCCN)C(=O)N3CCC(N)(CC3)C(O)=O
InChI
InChIKey=FWMNVWWHGCHHJJ-SKKKGAJSSA-N
InChI=1S/C36H53N7O6/c1-24(2)21-29(32(45)40-28(15-9-10-18-37)34(47)43-19-16-36(39,17-20-43)35(48)49)42-33(46)30(23-26-13-7-4-8-14-26)41-31(44)27(38)22-25-11-5-3-6-12-25/h3-8,11-14,24,27-30H,9-10,15-23,37-39H2,1-2H3,(H,40,45)(H,41,44)(H,42,46)(H,48,49)/t27-,28-,29-,30-/m1/s1
| Molecular Formula | C36H53N7O6 |
| Molecular Weight | 679.8493 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Difelikefalin (Korsuva™) is a synthetic peptide agonist of the kappa opioid receptor being developed by Cara Therapeutics for the treatment of pruritus. In August 2021, intravenous difelikefalin was approved in the USA for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD) in adults undergoing haemodialysis. Difelikefalin selectively acts on kappa opioid receptors in peripheral tissues, which contribute to pruritis and nociception. The activation of opioid receptors in peripheral neurons and keratinocytes reduces afferent (sensory) impulses towards the central nervous system, decreasing pain signals. Activating kappa opioid receptors on immune cells, including monocytes and T lymphocytes, decreases the release of pro-inflammatory chemicals such as prostaglandins.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL237 |
0.16 nM [null] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Korsuva Approved UseTreatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis. Launch Date2021 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
61.9 ng/mL |
5 μg/kg single, intravenous dose: 5 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
168.8 ng/mL |
15 μg/kg single, intravenous dose: 15 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
94 ng × h/mL |
5 μg/kg single, intravenous dose: 5 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
246 ng × h/mL |
15 μg/kg single, intravenous dose: 15 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
31 h |
unknown, intravenous |
DIFELIKEFALIN plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
2 h |
5 μg/kg single, intravenous dose: 5 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2 h |
15 μg/kg single, intravenous dose: 15 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIFELIKEFALIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
73% |
DIFELIKEFALIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
15 ug/kg single, intravenous Highest studied dose Dose: 15 ug/kg Route: intravenous Route: single Dose: 15 ug/kg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
Disc. AE: Anxiety, Injection site phlebitis... AEs leading to discontinuation/dose reduction: Anxiety Sources: Injection site phlebitis |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Gastrointestinal disorders, Nausea... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (1.3%) Sources: Nausea (0.4%) Dizziness (0.4%) Headache (0.4%) Anxiety (0.9%) Insomnia (0.9%) Mental status changes (0.9%) |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Gastrointestinal disorders, Nausea... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (0.5%) Sources: Nausea (0.5%) Dizziness (1.6%) Headache (0.5%) Psychiatric disorders (1.6%) Mental status changes (0.5%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Anxiety | Disc. AE | 15 ug/kg single, intravenous Highest studied dose Dose: 15 ug/kg Route: intravenous Route: single Dose: 15 ug/kg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
| Injection site phlebitis | Disc. AE | 15 ug/kg single, intravenous Highest studied dose Dose: 15 ug/kg Route: intravenous Route: single Dose: 15 ug/kg Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: |
| Dizziness | 0.4% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Headache | 0.4% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Nausea | 0.4% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Anxiety | 0.9% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Insomnia | 0.9% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Mental status changes | 0.9% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Gastrointestinal disorders | 1.3% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Gastrointestinal disorders | 0.5% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Headache | 0.5% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Mental status changes | 0.5% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Nausea | 0.5% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Dizziness | 1.6% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Psychiatric disorders | 1.6% Disc. AE |
0.5 ug/kg 3 times / week multiple, intravenous Recommended|Studied dose Dose: 0.5 ug/kg, 3 times / week Route: intravenous Route: multiple Dose: 0.5 ug/kg, 3 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214916Orig1s000MultidisciplineR.pdf#page=36 Page: 33 | 36 |
Sample Use Guides
Recommended dosage is 0.5 mcg/kg. Administer by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD treatment. Do not mix or dilute KORSUVA prior to administration. Administer within 60 minutes of syringe preparation.
Route of Administration:
Intravenous
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 23:35:57 GMT 2025
by
admin
on
Mon Mar 31 23:35:57 GMT 2025
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| Record UNII |
NA1U919MRO
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| Record Status |
Validated (UNII)
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| Record Version |
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Difelikefalin
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| Related Record | Type | Details | ||
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TARGET -> AGONIST |
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |
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