Endostatin

Endostatin is a 20-kDa C-terminal fragment derived from type XVIII collagen, functioning as an endogenous inhibitor of angiogenesis and tumor growth. It is produced through proteolytic cleavage of the carboxyl-terminal domain of collagen XVIII and is expressed in various organs, with particularly high levels in the liver, lung, and kidney. It is a potent inhibitor of angiogenesis by blocking proliferation and organization of endothelial cells into new vasculature, inhibits cell proliferation and migration, and induces apoptosis and cell cycle arrest in endothelial cells.

Inhibits vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation on VEGF receptor 2 (KDR/Flk-1), thereby blocking a key pathway for angiogenesis. Blocks activation of downstream kinases such as ERK (extracellular signal-regulated kinase), p38 MAPK (mitogen activated protein kinase), focal adhesion kinase (p125FAK). May also target E-selectin and inhibit matrix metalloproteinases MMPs 2, 9, and 13—enzymes involved in extracellular matrix remodeling during vessel formation.