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Identification
NamePeginesatide
Accession NumberDB08894
TypeSmall Molecule
GroupsApproved
Description

Peginesatide is a synthetic peptide attached to polyethylene glycol for the treatment of anemia. The polyethylene glycol moiety helps make the drug less immunogenic and prolongs its plasma half-life. Chemically, peginesatide is designed to mimic the pharmacological activity of erythropoietin, but is not a replica of the structure itself. Peginesatide consists of two 21-amino acid chains that are covalently bonded by a linker derived from iminodiacetic acid and β-alanine. FDA approved March 27, 2012.

Structure
Thumb
Synonyms
Erythropoiesis-Stimulating Agent (ESA)
Hematide
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OmontysTakeda Pharmaceutical Company Ltd.
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Peginesatide acetate
ThumbNot applicableDBSALT000136
Categories
UNIIJX56W9N61Q
CAS number913976-27-9
WeightNot Available
Chemical Formula(C2H4O)n(C2H4O)nC229H344N62O58S6
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
Pharmacology
IndicationPeginesatide is used for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis
PharmacodynamicsPeginesatide increases the reticulocyte count and levels of hemoglobin. It also increases RBC count, hematocrit, and soluble transferrin receptor protein in a dose-dependent manner.
Mechanism of actionPeginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro.
Related Articles
AbsorptionTmax, SubQ dose = 48 hours; Bioavailability, SubQ dose = 46%; Peginesatide does not accumulate when administered every 4 weeks following intravenous or subcutaneous administration.
Volume of distribution

IV dose, dialysis patients = 34.9 ± 13.8 mL/kg;

Protein bindingPeginesatide does not bind to serum albumin or lipoprotein as demonstrated in in-vitro studies.
Metabolism

Preclinical radiolabeled peginesatide study indicated that peginesatide is not metabolized.

Route of eliminationPeginesatide administered intravenously or subcutaneously is primarily excreted via urine. Most of the excreted dose is in the form of unchanged drug. Elimination from the plasma is biphasic and rapid from vascular compartments. In contrast, the drug is selectively retained in sites of erythropoiesis like the bone marrow.
Half lifeIV dose, healthy subjects = 25.0 ± 7.6 hours; SubQ, healthy subjects = 53.0 ± 17.7 hours; IV dose, dialysis patients = 47.9 ± 16.5 hours;
Clearance

Systemic clearance, IV dose, dialysis patients = 0.5 ± 0.2 mL/hr•kg

ToxicityThe most common adverse events (≥10%) are dyspnea, diarrhea, nausea, cough, and arteriovenous fistula site complication.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7084245 No2004-05-122024-05-12Us
US7414105 No2004-05-122024-05-12Us
US7528104 No2004-05-122024-05-12Us
US7550433 No2006-06-022026-06-02Us
US7919118 No2004-05-122024-05-12Us
US7919461 No2006-06-022026-06-02Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
pKa6.0 ± 0.3FDA label
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
References
Synthesis ReferenceNot Available
General References
  1. Schmid H: Peginesatide for the treatment of renal disease-induced anemia. Expert Opin Pharmacother. 2013 May;14(7):937-48. doi: 10.1517/14656566.2013.780695. Epub 2013 Mar 18. [PubMed:23506424 ]
  2. Woodburn KW, Holmes CP, Wilson SD, Fong KL, Press RJ, Moriya Y, Tagawa Y: Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats. Xenobiotica. 2012 Jul;42(7):660-70. doi: 10.3109/00498254.2011.649310. Epub 2011 Dec 22. [PubMed:22188389 ]
  3. Woodburn KW, Fong KL, Wilson SD, Sloneker S, Strzemienski P, Solon E, Moriya Y, Tagawa Y: Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration. Drug Metab Dispos. 2013 Apr;41(4):774-84. doi: 10.1124/dmd.112.048033. Epub 2013 Jan 14. [PubMed:23318685 ]
External Links
ATC CodesB03XA04
AHFS Codes
  • 20:16
PDB EntriesNot Available
FDA labelDownload (272 KB)
MSDSNot Available
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
stimulator
General Function:
Identical protein binding
Specific Function:
Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.Isoform EPOR-T acts as a dominant-negative receptor of EPOR-mediated signaling.
Gene Name:
EPOR
Uniprot ID:
P19235
Molecular Weight:
55064.725 Da
References
  1. Woodburn KW, Fong KL, Wilson SD, Sloneker S, Strzemienski P, Solon E, Moriya Y, Tagawa Y: Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration. Drug Metab Dispos. 2013 Apr;41(4):774-84. doi: 10.1124/dmd.112.048033. Epub 2013 Jan 14. [PubMed:23318685 ]
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Drug created on June 01, 2013 16:45 / Updated on June 25, 2016 01:51