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 chemical formula||C294H342F13N107Na28O188P28[C2H4O]2n|
|Protein average weight||50000.0 Da (approximate)|
|External IDs||Not Available|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
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For the treatment of neovascular (wet) age-related macular degeneration.
Pegaptanib 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 action|
Pegaptanib 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.
In 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 binding||Not Available|
Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.
|Route of elimination|
It 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.
In 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.
It 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.
|Pharmacogenomic Effects/ADRs||Not Available|
|Food Interactions||Not Available|
|Synthesis Reference||Not Available|
|ATC Codes||S01LA03 — Pegaptanib|
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (99.6 KB)|
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|Experimental Properties||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
|External Descriptors||Not Available|
- Pharmacological action
- 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:
- Uniprot ID:
- Molecular Weight:
- 103133.62 Da
- Vinores SA: Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. [PubMed:17717967 ]