ZM323881 inhibits VEGF-A-induced endothelial cell proliferation (IC50 = 8 nM) and VEGF-R2 tyrosine phosphorylation (IC50 < 2 nM).
Vascular endothelial growth factor (VEGF) increases vascular permeability and angiogenesis in many pathological conditions, such as cancer, arthritis, and diabetes. VEGF activates VEGF-Receptor 1 (VEGF-R1) and VEGF-Receptor 2 (VEGF-R2) that autophosphorylate to initiate a signaling cascade resulting in angiogenesis and increased microvascular permeability. ZM323881 is a potent and selective inhibitor of VEGF-R2 tyrosine kinase.
In vitro: ZM323881 was found to inhibit VEGF-A-induced endothelial cell proliferation (IC50 = 8 nM) and VEGF-R2 tyrosine phosphorylation in vitro (IC50 < 2 nM) [1].
In vivo: VEGF-Amediated increases in vascular permeability in perfused mesenteric microvessels in vivo were reversibly abolished by both ZM323881 and the class III receptor tyrosine kinase inhibitor PTK787/ZK222584, suggesting that VEGF-R2 phosphorylation is necessary for VEGF-A-mediated increases in microvascular permeability in vivo [1].
Clinical trials: There is no clinical data are available currenlty.
Reference:
[1] Whittles CE, Pocock TM, Wedge SR, Kendrew J, Hennequin LF, Harper SJ, Bates DO. ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation. 2002;9(6):513-22.