| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 500mg | |||
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| Other Sizes |
| Targets |
Difelikefalin targets the kappa opioid receptor (KOR), a G protein-coupled receptor expressed in peripheral sensory neurons and immune cells. Activation of KOR by difelikefalin inhibits the release of pruritogenic mediators and reduces itch signaling. The compound is peripherally restricted, meaning it does not cross the blood-brain barrier, which minimizes central nervous system side effects such as dysphoria or sedation.
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| ln Vitro |
In vitro, difelikefalin binds to and activates the kappa opioid receptor (KOR). The compound shows selectivity for KOR over mu and delta opioid receptors. Functional assays measuring cAMP inhibition or β-arrestin recruitment are used to assess agonist activity. The compound's peripheral restriction is confirmed by in vitro permeability assays.
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| ln Vivo |
In vivo, difelikefalin has demonstrated efficacy in animal models of itch, including models of chronic kidney disease-associated pruritus. The compound reduces scratching behavior in rodent models. In clinical trials, difelikefalin has shown significant reduction in itch intensity and improvement in quality of life in patients with CKD-aP. The compound is administered intravenously or topically.
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| Enzyme Assay |
In vitro KOR binding assays for difelikefalin are performed using membrane preparations from cells expressing recombinant human KOR. Competitive binding experiments are conducted with radiolabeled KOR ligands. Various concentrations of the test compound are incubated with the receptor membranes, and bound radioactivity is measured. IC₅₀ values are calculated from displacement curves.
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| Cell Assay |
In vitro cellular functional assays for difelikefalin involve cell lines expressing KOR. The compound's ability to inhibit forskolin-stimulated cAMP accumulation is measured using HTRF or ELISA-based kits. Alternatively, β-arrestin recruitment assays can be performed. EC₅₀ values for KOR activation are determined from concentration-response curves. The compound's selectivity for KOR over mu and delta receptors is assessed.
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| Animal Protocol |
In vivo efficacy studies for difelikefalin are conducted in rodent models of itch, such as the compound 48/80-induced scratching model or the chronic kidney disease model. The compound is administered intravenously or subcutaneously. Scratching behavior is monitored and quantified. The compound's ability to reduce itch and improve skin condition is evaluated.
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| ADME/Pharmacokinetics |
Difelikefalin is administered intravenously and has a short half-life. The compound is peripherally restricted and does not cross the blood-brain barrier, minimizing central side effects. It is metabolized by peptidases and excreted in urine and feces. The pharmacokinetic profile supports intravenous administration in clinical settings.
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| Toxicity/Toxicokinetics |
Preclinical and clinical toxicology studies of difelikefalin indicate that the compound is generally well-tolerated. Common adverse events include nausea, dizziness, and somnolence. The compound has a favorable safety profile with low risk of opioid-related central side effects due to its peripheral restriction. Long-term safety studies are ongoing.
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| Additional Infomation |
See also: Difelikefalin (with active fraction).
Difelikefalin acetate (Korsuva®) is a selective kappa opioid receptor (KOR) agonist used for its antipruritic effects. It is indicated for the treatment of chronic kidney disease-associated pruritus (CKD-aP) in adult patients undergoing hemodialysis. The compound is a synthetic peptide that is peripherally restricted, minimizing central nervous system side effects. This product is for research use only and is not intended for human therapeutic use. |
| Molecular Weight |
739.901289701462
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|---|---|
| Exact Mass |
739.426
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| CAS # |
1024829-44-4
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| PubChem CID |
91864509
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
53
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
4
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| SMILES |
OC(C1(CCN(C([C@@H](CCCCN)NC([C@@H](CC(C)C)NC([C@@H](CC2C=CC=CC=2)NC([C@@H](CC2C=CC=CC=2)N)=O)=O)=O)=O)CC1)N)=O.OC(C)=O
|
| InChi Key |
MZWHRPKAHCWTOI-KGURMGBCSA-N
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| InChi Code |
InChI=1S/C36H53N7O6.C2H4O2/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;1-2(3)4/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);1H3,(H,3,4)/t27-,28-,29-,30-;/m1./s1
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| Chemical Name |
acetic acid;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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3515 mL | 6.7577 mL | 13.5153 mL | |
| 5 mM | 0.2703 mL | 1.3515 mL | 2.7031 mL | |
| 10 mM | 0.1352 mL | 0.6758 mL | 1.3515 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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