ZM306416 hydrochloride, VEGFR1/2 tyrosine kinase activity inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The VEGF receptors—VEGF Receptor 1 (Flt-1) VEGF Receptor 2 (KDR/Flk-1) and VEGF Receptor 3 (Flt-4)—are tyrosine kinase receptors that mediate vascular endothelial growth factor (VEGF) signaling. These receptors vary in molecular mass with VEGF Receptor 1 being approximately 180 kDa VEGF Receptor 2 about 200 - 210 kDa and VEGF Receptor 3 around 195 - 200 kDa. They are expressed on the surface of various cells primarily vascular endothelial cells where they regulate different functions related to angiogenesis and lymphangiogenesis.

Biological function summary

These receptors play roles in modulating vascular permeability endothelial cell proliferation and blood vessel formation. They are part of complexes that include ligands such as various VEGF isoforms. VEGF Receptor 2 is the principal mediator of VEGF-induced endothelial cell responses. VEGF Receptor 1 serves as a decoy receptor to modulate the availability of VEGF for VEGF Receptor 2 whilst VEGF Receptor 3 mainly regulates lymphatic endothelial cell functions.

Pathways

These receptors are central to the VEGF signaling pathway which plays a role in angiogenesis and vasculogenesis. The pathway involves a cascade where VEGF binding leads to receptor dimerization and phosphorylation of intracellular domains activating downstream pathways like the MAPK and PI3K/Akt pathways. These receptors interact with various proteins including growth factors and other signaling molecules to ensure proper vascular function and adaptation.

Dysregulation of VEGF receptor signaling is implicated in cancer and retinal diseases. Overexpression or aberrant activation of VEGF Receptor 2 in particular is associated with tumor-induced angiogenesis allowing tumors to grow their own blood supply. In eye diseases like age-related macular degeneration improper VEGF signaling contributes to abnormal blood vessel formation. Other proteins such as neuropilins modulate these interactions serving as co-receptors to alter binding affinity and signaling output in disease contexts.