U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of DIFELIKEFALIN

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

HIDE SMILES / InChI

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Korsuva

Approved Use

Treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis.

Launch Date

2021
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
73%
DIFELIKEFALIN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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
Injection site phlebitis
Sources:
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%)
Nausea (0.4%)
Dizziness (0.4%)
Headache (0.4%)
Anxiety (0.9%)
Insomnia (0.9%)
Mental status changes (0.9%)
Sources:
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%)
Nausea (0.5%)
Dizziness (1.6%)
Headache (0.5%)
Psychiatric disorders (1.6%)
Mental status changes (0.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [Inhibition 10 uM]
no [Inhibition 10 uM]
no [Inhibition 10 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Tox targets

Tox targets

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
Difelikefalin activates KOR in HEK293 cells expressing the human receptor (EC50 = 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50 = 0.048 nM).
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:35:57 GMT 2025
Edited
by admin
on Mon Mar 31 23:35:57 GMT 2025
Record UNII
NA1U919MRO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
difelikefalin [INN]
Preferred Name English
DIFELIKEFALIN
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
CR-845
Code English
FE202845
Code English
DIFELIKEFALIN [USAN]
Common Name English
MR-13A9
Code English
Difelikefalin [WHO-DD]
Common Name English
FE-202845
Code English
DIFELIKEFALIN ACETATE [JAN]
Common Name English
MR13A9
Code English
4-AMINO-1-(D-PHENYLALANYL-D-PHENYLALANYL-D-LEUCYL-D-LYSYL)PIPERIDINE-4-CARBOXYLIC ACID
Systematic Name English
4-PIPERIDINECARBOXYLIC ACID, N1-(D-PHENYLALANYL-D-PHENYLALANYL-D-LEUCYL-D-LYSYL)-4-AMINO-
Code English
CR845
Code English
Code System Code Type Description
EPA CompTox
DTXSID401032896
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
DAILYMED
NA1U919MRO
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
RXCUI
2569089
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
PUBCHEM
24794466
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
INN
10179
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
EVMPD
SUB195302
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
CAS
1024828-77-0
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
DRUG BANK
DB11938
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
FDA UNII
NA1U919MRO
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
SMS_ID
100000181568
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
NCI_THESAURUS
C174752
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
USAN
DE-165
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
WIKIPEDIA
Difelikefalin
Created by admin on Mon Mar 31 23:35:57 GMT 2025 , Edited by admin on Mon Mar 31 23:35:57 GMT 2025
PRIMARY
Related Record Type Details
TARGET -> AGONIST
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY