ZM323881 hydrochloride (ZM 323881 HCl) is a potent and selective VEGFR2 inhibitor.

At concentrations below 1 μM, ZM323881 inhibits the proliferation of neural stem cells stimulated by VEGF in a dose-dependent manner. It impedes the activation of extracellular signal-regulated kinase, p38, Akt, and endothelial nitric oxide synthase (eNOS) through VEGF blockade at 1 μM, without suppressing the expression of the VEGFR-1 specific ligand, placental growth factor (PlGF), in human aortic endothelial cells (HAECs). Additionally, 1 μM ZM323881 disrupts VEGF-induced membrane extension, cell migration, and tube formation in HAECs and reverses the phosphorylation of CrkII and its SRC homology 2 domain-binding protein p130Cas, key in regulating endothelial cell migration. ZM323881 inhibits the proliferation of HUVEC cells induced by VEGF-A, EGF, and bFGF, with IC50 values of 8 nM, 1.9 μM, and 1.6 μM respectively. At 10 nM, ZM323881 eradicates the increase in vascular permeability mediated by VEGF-A in the mesenteric microvasculature of male leopards. Furthermore, 10 nM ZM323881 completely obstructs VEGF-induced promoter activity and Hif-1α protein accumulation in VEGF-stimulated SCC-9 cells.