Structure of VEGFA

Vascular Endothelial Growth Factor A (VEGFA) is a key member of the VEGF family and plays a crucial role in angiogenesis and vascular permeability.

• Dimeric glycoprotein: VEGFA forms a homodimer via disulfide bonds.
• Isoforms: Alternative splicing generates multiple isoforms, including VEGFA121, VEGFA165, VEGFA189, and VEGFA206, each with different receptor-binding properties and tissue distribution.
• Receptor Binding: VEGFA binds to VEGFR-1 (Flt-1)and VEGFR-2 (KDR/Flk-1) to trigger downstream signaling.

Function of VEGFA

• Angiogenesis: Stimulates endothelial cell proliferation and migration.
• Vascular Permeability: Increases vascular leakage, crucial in wound healing and tumor growth.
• Hematopoiesis: Regulates blood vessel formation in the bone marrow.
• Pathological Roles: Overexpression is linked to cancer, diabetic retinopathy, and age-related macular degeneration (AMD).

VEGFA Signaling Pathway

• Ligand Binding: VEGFA binds to VEGFR-2, initiating dimerization and autophosphorylation.
• Downstream Signaling:

• PI3K-AKT Pathway: Promotes cell survival.
• Ras-Raf-MEK-ERK Pathway: Induces endothelial cell proliferation.
• PLCγ-PKC Pathway: Enhances vascular permeability.
• Endothelial Activation: Leads to new blood vessel formation and increased permeability.

Market Prospects of VEGFA Inhibitors

• The global VEGFA-targeted therapy marketwas valued at $9.2 billion in 2022 and is projected to reach $15 billion by 2030.
• Key growth drivers: Rising incidence of cancer, AMD, and diabetic retinopathy.
• Major companies: Roche, Novartis, Regeneron, Bayer, and Eli Lilly.
• Future trends: Combination therapies, biosimilars, and gene therapy approaches.

FDA-Approved VEGFA Inhibitors

VEGFA inhibitors continue to be a cornerstone of anti-angiogenic therapy, with ongoing research into biosimilars, novel formulations, and combination regimens for broader clinical applications.

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