alexa Vascular Endothelial Growth Factor (VEGF) Biochemistry and Development of Inhibitory Drugs


Journal of Clinical & Experimental Ophthalmology

Author(s): Stewart MW

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Angiogenesis plays a critical role in human growth and development, as well as tissue repair and maintenance. Though angiogenesis can be stimulated by several metabolites and growth factors, vascular endothelial growth factor (VEGF) appears to be critical for all new vessel growth. VEGF includes several molecules that are classified according to structure and binding characteristics into the following groupings: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor. VEGF binds with 3 trans-membrane receptors (VEGFR1, VEGFR2, and VEGFR3) each of which initiates downstream signaling through intracellular tyrosine kinase activity. Binding to receptors is amplified by neuropilins, which interact with the heparin binding domain of VEGF and favorably present the receptor binding site to the receptor binding domain. Though VEGF may be synthesized by several cell types, the molecule’s primary target is vascular endothelial cells. VEGF exerts several effects on its target tissues: mitogenicity, vascular hyperpermeability, migration, survival factor, vasodilator, and chemoattraction. Two VEGF binding drugs (pegaptanib and ranibizumab) have been developed specifically for intraocular use. Aflibercept is being developed for both ophthalmologic and oncologic use, and bevacizumab has been used off-label to treat ocular diseases. Each of these drugs binds diffusible VEGF, thereby preventing its binding to the trans-membrane receptors. The drugs have undergone extensive pre-clinical trials in animal models.

This article was published in Current Drug Therapy and referenced in Journal of Clinical & Experimental Ophthalmology

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