difelikefalin

{{Short description|Chemical compound}}

{{Infobox drug

| image = Difelikefalin.svg

| image_class = skin-invert-image

| width = 250

| alt =

| caption =

| pronounce =

| tradename = Korsuva

| Drugs.com =

| MedlinePlus =

| DailyMedID = Difelikefalin

| pregnancy_AU = B1

| pregnancy_AU_comment = {{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=21 December 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=2 January 2023 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}

| pregnancy_category=

| routes_of_administration = Intravenous

| class = Kappa opioid receptor agonist

| ATC_prefix = V03

| ATC_suffix = AX04

| ATC_supplemental =

| legal_AU = S4

| legal_AU_comment = {{cite web | title=Korsuva | website=Therapeutic Goods Administration (TGA) | date=25 November 2022 | url=https://www.tga.gov.au/resources/auspmd/korsuva | access-date=7 April 2023 | archive-date=5 February 2023 | archive-url=https://web.archive.org/web/20230205203429/https://www.tga.gov.au/resources/auspmd/korsuva | url-status=live }}{{cite web |url=https://www.tga.gov.au/resources/auspar/auspar-korsuva |website=Therapeutic Goods Administration (TGA) |title=AusPAR: Korsuva |date=November 2023 |archive-url=https://web.archive.org/web/20241101010801/https://www.tga.gov.au/resources/auspar/auspar-korsuva |archive-date=1 November 2024 |url-status=live}}

| legal_BR =

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = {{cite web|url=https://pdf.hres.ca/dpd_pm/00066996.PDF|access-date=7 April 2023|website=Health Canada|title=Product monograph|archive-date=1 October 2022|archive-url=https://web.archive.org/web/20221001060048/https://pdf.hres.ca/dpd_pm/00066996.PDF|url-status=live}}{{cite web | title=Summary Basis of Decision - Korsuva | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00615&lang=en | access-date=24 January 2023 | archive-date=24 January 2023 | archive-url=https://web.archive.org/web/20230124031805/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00615&lang=en | url-status=live }}{{cite web | title=Details for: Korsuva | website=Health Canada | date=6 February 2023 | url=https://dhpp.hpfb-dgpsa.ca/dhpp/resource/101892 | access-date=3 March 2024 | archive-date=3 March 2024 | archive-url=https://web.archive.org/web/20240303063930/https://dhpp.hpfb-dgpsa.ca/dhpp/resource/101892 | url-status=live }}

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK =

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Korsuva- difelikefalin injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c7b81f2-0fd3-47cb-8b0f-185e07f19c87 | access-date=12 September 2021 | archive-date=12 September 2021 | archive-url=https://web.archive.org/web/20210912221530/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c7b81f2-0fd3-47cb-8b0f-185e07f19c87 | url-status=live }}

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Kapruvia EPAR | website=European Medicines Agency (EMA) | date=22 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kapruvia | access-date=28 April 2022 | archive-date=6 May 2022 | archive-url=https://web.archive.org/web/20220506032536/https://www.ema.europa.eu/en/medicines/human/EPAR/kapruvia | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

| legal_UN =

| legal_UN_comment =

| legal_status =

| bioavailability = 100% (IV)

| protein_bound =

| metabolism = Not metabolized

| metabolites =

| onset =

| elimination_half-life = 2 hours

| duration_of_action =

| excretion = Excreted as unchanged
drug via bile and urine

| index2_label = as salt

| CAS_number = 1024828-77-0

| CAS_number2 = 1024829-44-4

| CAS_supplemental =

| PubChem = 24794466

| PubChem2 = 91864509

| IUPHAR_ligand =

| DrugBank = DB11938

| DrugBank2 = DBSALT003191

| ChemSpiderID = 44208824

| ChemSpiderID2 =

| UNII = NA1U919MRO

| UNII2 = 0P70AR5BYB

| KEGG = D11111

| KEGG2 = D10890

| ChEBI =

| ChEMBL = 3989915

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = CR845, FE-202845, D-Phe-D-Phe-D-Leu-D-Lys-[γ-(4-N-piperidinyl)amino carboxylic acid]{{cite journal | vauthors = Janecka A, Perlikowska R, Gach K, Wyrebska A, Fichna J | title = Development of opioid peptide analogs for pain relief | journal = Current Pharmaceutical Design | volume = 16 | issue = 9 | pages = 1126–1135 | year = 2010 | pmid = 20030621 | doi = 10.2174/138161210790963869 }}

| 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

| C=36 | H=53 | N=7 | O=6

| 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

| SMILES2 = 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

| StdInChI = 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

| StdInChI2 = 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

| StdInChI_comment =

| StdInChIKey = FWMNVWWHGCHHJJ-SKKKGAJSSA-N

| StdInChIKey2 = MZWHRPKAHCWTOI-KGURMGBCSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

}}

Difelikefalin, sold under the brand name Korsuva, is an opioid peptide used for the treatment of moderate to severe itch. It acts as a peripherally-restricted, highly selective agonist of the κ-opioid receptor (KOR).{{cite book| vauthors = Chalmers D | chapter = Peripheral kappa agonists| veditors = Sinatra RS, Jahr JS, Watkins-Pitchford JM |title=The Essence of Analgesia and Analgesics| chapter-url = https://books.google.com/books?id=ZwPIjKg0XukC&pg=PA490|date=14 October 2010|publisher=Cambridge University Press|isbn=978-1-139-49198-3|pages=490–491}}{{cite book| vauthors = Apfelbaum J |title=Ambulatory Anesthesia, An Issue of Anesthesiology Clinics|url=https://books.google.com/books?id=IlTOAwAAQBAJ&pg=PT190|date=8 September 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-29934-3|pages=190–}}{{cite book| vauthors = Leslie TA, Greavers MW, Yosipovitch G | chapter = Current Topical and Systemic Therapies for Itch | veditors = Cowan A, Yosipovitch G |title=Pharmacology of Itch| chapter-url = https://books.google.com/books?id=Jl0SCAAAQBAJ&pg=PA307|date=10 April 2015|publisher=Springer|isbn=978-3-662-44605-8|pages=307–}}{{cite book | vauthors = Goli V, Pryde D, Omoto K | chapter = Oral Opioids| veditors = Allerton C |title=Pain Therapeutics: Current and Future Treatment Paradigms| chapter-url = https://books.google.com/books?id=zUINAgAAQBAJ&pg=PA56|year=2013|publisher=Royal Society of Chemistry|isbn=978-1-84973-645-9|pages=56–}}

Difelikefalin acts as an analgesic by activating KORs on peripheral nerve terminals and KORs expressed by certain immune system cells. Activation of KORs on peripheral nerve terminals results in the inhibition of ion channels responsible for afferent nerve activity, causing reduced transmission of pain signals, while activation of KORs expressed by immune system cells results in reduced release of proinflammatory, nerve-sensitizing mediators (e.g., prostaglandins).

Difelikefalin was approved for medical use in the United States in August 2021.{{cite web | title=Korsuva: FDA-Approved Drugs | website=U.S. Food and Drug Administration | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214916 | access-date=24 August 2021 | archive-date=25 August 2021 | archive-url=https://web.archive.org/web/20210825050736/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214916 | url-status=live }}{{cite press release | title=Vifor Pharma and Cara Therapeutics announce U.S. FDA approval of Korsuva injection for the treatment of moderate-to-severe pruritus in hemodialysis patients | publisher=Vifor Pharma | via=Business Wire | date=24 August 2021 | url=https://www.businesswire.com/news/home/20210823005635/en/Vifor-Pharma-and-Cara-Therapeutics-announce-U.S.-FDA-approval-of-KORSUVA%E2%84%A2-injection-for-the-treatment-of-moderate-to-severe-pruritus-in-hemodialysis-patients | access-date=24 August 2021 | archive-date=24 August 2021 | archive-url=https://web.archive.org/web/20210824213538/https://www.businesswire.com/news/home/20210823005635/en/Vifor-Pharma-and-Cara-Therapeutics-announce-U.S.-FDA-approval-of-KORSUVA%E2%84%A2-injection-for-the-treatment-of-moderate-to-severe-pruritus-in-hemodialysis-patients | url-status=live }} The U.S. Food and Drug Administration considers it to be a first-in-class medication.{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. Food and Drug Administration (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download | url-status=live }} {{PD-notice}}