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Identification
NamePegaptanib
Accession NumberDB04895
TypeBiotech
GroupsApproved, Investigational
Description

Pegaptanib is a polynucleotide aptamer. Pegaptanib specifically binds to VEGF 165, a protein that plays a critical role in angiogenesis (the formation of new blood vessels) and increased permeability (leakage from blood vessels), two of the primary pathological processes responsible for the vision loss associated with neovascular AMD. [Wikipedia]

Protein structureDb04895
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Protein chemical formulaC294H342F13N107Na28O188P28[C2H4O]2n
Protein average weight50000.0 Da (approximate)
SequencesNot Available
Synonyms
EYE 001
NX 1838
NX1838
Pegaptanib Octasodium
Pegaptanib sodium
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Macugeninjection, solution3.47 mg/mLintravitrealEyetech Inc.2004-12-17Not applicableUs
Macugensolution0.3 mgintravitrealPfizer Canada Inc2005-08-262014-09-04Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII3HP012Q0FH
CAS number222716-86-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of neovascular (wet) age-related macular degeneration.
PharmacodynamicsPegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist. VEGF is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells. VEGF induces angiogenesis, and increases vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD), a leading cause of blindness. VEGF has been implicated in blood retinal barrier breakdown and pathological ocular neovascularization.
Mechanism of actionPegaptanib sodium is a pegylated aptamer, a modified oligonucleotide, which adopts a three- dimensional conformation that enables it to bind to extracellular VEGF with high affinity and selectivity. Pegaptanib sodium binds to the major pathological VEGF isoform, extracellular VEGF165, with high affinity (Kd = 200 pM) and specificity, thereby inhibiting VEGF165 binding to its VEGF receptors. In contrast virtually no binding of the non-pegylated aptamer to VEGF121 or the VEGF -related proteins VEGF-B, VEGF-C and placental growth factor (PlGF) was detected using invitro filter binding assays. Pegaptanib sodium does not bind significantly to VEGF121. In animal models, VEGF164 (the rodent counterpart of human VEGF165) was specifically upregulated in disease. The selective inhibition of VEGF164 with pegaptanib sodium proved as effective at suppressing pathological neovascularization as pan-VEGF inhibition7, however pegaptanib sodium spared the normal vasculature whereas pan-VEGF inhibition did not.
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AbsorptionIn animals, pegaptanib is slowly absorbed into the systemic circulation from the eye after intravitreous administration.
Volume of distribution

It is distributed into vitreous fluid, retina, aqueous fluid, and kidneys. As well, it has been shown to cross the placenta in mice but whether or not it crosses the placenta in humans is unknown.

Protein bindingNot Available
Metabolism

Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.

Route of eliminationIt is excreted primarily in urine as unchanged drug and also as metabolites. There is no dosage adjustment required for patients with renal impairment although it must be noted that not many studies have looked at patients with a creatinine clearance of 30mL/min.
Half lifeIn humans, after a 3 mg monocular dose (10 times the recommended dose), the average (± standard deviation) apparent plasma half-life of pegaptanib is 10 (± 4) days.
ClearanceNot Available
ToxicityIt is not known if pegaptanib is safe in pregnant women or if it is excreted in breast milk. Likewise, no studies have been done in the pediatric population. Most adverse events elated to the drug are ocular however non-ocular adverse events related to the drug or the injection procedure also occurred, among which headaches and rhinorrhoea appeared in more than 1% of patients. Pegaptanib is contraindicated when the patient has an ocular or periocular infection.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravitreal3.47 mg/mL
Solutionintravitreal0.3 mg
Prices
Unit descriptionCostUnit
Macugen 0.3 mg/0.09 ml1194.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2269072 No2006-02-142017-10-17Canada
US5932462 No1996-08-032016-08-03Us
US6011020 No1997-01-042017-01-04Us
US6147204 No1993-06-112010-06-11Us
Properties
StateLiquid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Vinores SA: Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. [PubMed:17717967 ]
  2. Wylegala E, Teper SJ: [VEGF in age-related macular degeneration. Part II. VEGF inhibitors use in age-related macular degeneration treatment]. Klin Oczna. 2007;109(1-3):97-100. [PubMed:17687925 ]
  3. Bakri SJ, Pulido JS, McCannel CA, Hodge DO, Diehl N, Hillemeier J: Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye (Lond). 2009 Jan;23(1):181-5. Epub 2007 Aug 10. [PubMed:17693999 ]
External Links
ATC CodesS01LA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (99.6 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
PegloticaseThe therapeutic efficacy of Pegaptanib can be decreased when used in combination with Pegloticase.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in ...
Gene Name:
NRP1
Uniprot ID:
O14786
Molecular Weight:
103133.62 Da
References
  1. Vinores SA: Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. [PubMed:17717967 ]
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Drug created on October 21, 2007 16:23 / Updated on July 27, 2016 01:56