Difelikefalin acetateProduct ingredient for Difelikefalin
- Name
- Difelikefalin acetate
- Drug Entry
- Difelikefalin
Difelikefalin (CR845) is an agonist of kappa opioid receptors (KORs) useful in the treatment of pruritus secondary to chronic kidney disease. KORs were first associated with itching in 1984.1 Further investigations revealed that dynorphins, endogenous agonists of KORs, work to inhibit the itching sensation at the spinal cord level, and scratching could be elicited in mouse models with the administration of KOR antagonists.1 These revelations led to the study of KOR agonists as a potential treatment option in patients suffering from pruritic conditions.
Pruritus associated with chronic kidney disease (also called uremic pruritus) affects 50-60% of all patients on dialysis and 25% of non-dialysis patients with chronic kidney disease.2,3 The clinical burden of uremic pruritus in this patient population is being increasingly recognized as contributing to a significant reduction in patient quality of life, poor outcomes, and even mortality.3 Options for therapy are limited - with no FDA-approved treatments, off-label gabapentin was the most evidence-based and widely available treatment.3
Difelikefalin received FDA approval in August 2021 (under the brand name Korsuva), becoming the first FDA-approved therapy for patients with chronic kidney disease suffering from uremic pruritus.5,4 Difelikefalin was later approved by the EMA in April 2022 for the same indication.7
- Accession Number
- DBSALT003191
- Structure
- Synonyms
- Not Available
- External IDs
- CR-845 ACETATE
- UNII
- 0P70AR5BYB
- CAS Number
- 1024829-44-4
- Weight
- Average: 739.915
Monoisotopic: 739.426861823 - Chemical Formula
- C38H57N7O8
- InChI Key
- MZWHRPKAHCWTOI-KGURMGBCSA-N
- InChI
- 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
- IUPAC Name
- 4-amino-1-[(2R)-6-amino-2-[(2R)-2-[(2R)-2-[(2R)-2-amino-3-phenylpropanamido]-3-phenylpropanamido]-4-methylpentanamido]hexanoyl]piperidine-4-carboxylic acid; acetic acid
- SMILES
- CC(O)=O.CC(C)C[C@@H](NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](N)CC1=CC=CC=C1)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O
- External Links
- ChemSpider
- 64853867
- Predicted Properties
Property Value Source Water Solubility 0.0103 mg/mL ALOGPS logP -0.86 ALOGPS logP -1.7 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 1.92 Chemaxon pKa (Strongest Basic) 10.26 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 7 Chemaxon Polar Surface Area 222.97 Å2 Chemaxon Rotatable Bond Count 18 Chemaxon Refractivity 185.74 m3·mol-1 Chemaxon Polarizability 73.95 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon