Details of the Drug

General Information of Drug (ID: DMHZBEO)

Drug Name

Difelikefalin

Synonyms

UNII-NA1U919MRO; NA1U919MRO; MR13A9; 1024828-77-0; FE202845; Difelikefalin [INN]; Difelikefalin [USAN:INN]; SEQ ID NO: 2; GTPL9044; CHEMBL3989915; SCHEMBL10316464; BDBM235785; DB11938; FE-202845; US9359399, 2; D-Phe-D-Phe-D-Leu-D-Lys-[gamma-(4-N-piperidinyl)amino carboxylic acid]; 4-Piperidinecarboylic acid, 4-amino-1-(D-phenylalanyl-D-phenylalanyl-D-leucyl-D-lysyl)-; 4-Piperidinecarboxylic acid, N1-(D-phenylalanyl-D-phenylalanyl-D-leucyl-D-lysyl)-4-amino-; 4-Piperidinecarboxylic acid, N1-(D

Indication

Disease Entry	ICD 11	Status	REF
Pruritus	EC90	Phase 3	[1]

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

679.8

Topological Polar Surface Area (xlogp)

-0.6

Rotatable Bond Count (rotbonds)

18

Hydrogen Bond Donor Count (hbonddonor)

7

Hydrogen Bond Acceptor Count (hbondacc)

9

ADMET Property

Bioavailability: The bioavailability of drug is 100% [2]
Elimination: Approximately 11% of the dose was excreted in the urine, 59% in the feces, and 20% in the dialysate [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 23 - 31 hours [2]
Metabolism: The drug is not metabolised [2]
Vd: The volume of distribution (Vd) of drug is 0.238 L/kg [2]

Chemical Identifiers

Formula: C36H53N7O6
IUPAC Name: 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
Canonical SMILES: CC(C)C[C@H](C(=O)N[C@H](CCCCN)C(=O)N1CCC(CC1)(C(=O)O)N)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@@H](CC3=CC=CC=C3)N
InChI: 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
InChIKey: FWMNVWWHGCHHJJ-SKKKGAJSSA-N

Cross-matching ID

PubChem CID: 24794466
CAS Number: 1024828-77-0
DrugBank ID: DB11938
TTD ID: D0K3OK

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Agonist	[1]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Pruritus

ICD Disease Classification

EC90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor kappa (OPRK1)	DTT	OPRK1	9.17E-01	0.04	0.1

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	FDA Approved Drug Products: Korsuva (difelikefalin) for intravenous injection
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
4	Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
5	In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
6	Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
7	Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
8	Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
9	Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.
10	Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
11	Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior. Anesthesiology. 2011 December; 115(6): 1363-1381.
12	Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997 Oct;6(10):1351-68.