Zenidolol

Zenidolol (ICI-118551) is a selective β2-adrenergic receptor antagonist with K_i values of Zenidolol for β2, β1 and β3 adrenergic receptors of 0.7, 49.5 and 611 nM, respectively. Zenidolol exerts antitumor effects via inducing apoptosis, inhibiting tumor sphere formation, and downregulating the HIF pathway by blocking β2-AR on tumor cells. Zenidolol exhibits a unique pulmonary vessel-specific vasodilatory effect in mouse models. Zenidolol can be used as an intraocular pressure-lowering agent in ophthalmic disease research^{[1][2][3][4][5]}. In Vitro:Zenidolol (0-200 μM; 48 h) reduces the cell viability of primary cultured hemangioblastomas derived from VHL in a dose-dependent manner, and exhibits higher specificity for HB cells compared with HUVECs^[1].
Zenidolol (100 μM; 7 days) inhibits glomeruloid body formation in primary cultures of hemangioblastomas derived from VHL tumors^[1].
Zenidolol (100 μM; 6 h) inhibits endothelial cell migration and angiogenesis in human umbilical vein endothelial cells (HUVECs)^[1].
Zenidolol (100 μM; 48 h) attenuates hypoxia-induced nuclear translocation of HIF-1α in human umbilical vein endothelial cells (HUVECs) and primary cultures of VHL-derived hemangioblastomas^[1].
Zenidolol (100 μM; 72 h) induces apoptosis in primary cultures of VHL-derived hemangioblastomas by increasing caspase 3/7/9 activity and upregulating the pro-apoptotic gene BAX^[1].
Zenidolol (100 μM; 48-72 h) inhibits the expression of AQP-1, a HIF target gene, in primary cultures of hemangioblastoma derived from VHL^[1].
Zenidolol (10 μM) induces nitric oxide production in bovine pulmonary artery endothelial cells and promotes phosphorylation of the Ser1177 site of endothelial nitric oxide synthase^[4]. In Vivo:Zenidolol (5-500 μg/kg; i.v.; cumulative administration) is a potent β2-selective adrenergic receptor antagonist. In anesthetized Beagle dogs, its affinity for vascular β2-receptors is at least 250-fold higher than that for cardiac β1-receptors^[2].
Zenidolol (50-1000 μg/kg; i.v.; cumulative administration) at doses that block vascular β2-adrenoceptors does not affect the cardiac responses to sympathetic nerve stimulation in anesthetized Beagle dogs, whereas the high dose (1 mg/kg) inhibits SNS-induced heart rate elevation^[2].
Zenidolol (0.25-2.0%, 30 μg/kg; topical ocular administration, subcutaneous administration; single dose) is a potent ocular hypotensive agent with extremely low cardiac side effects, and it weakly blocks cardiac β-adrenergic receptor-mediated responses^[3].
Zenidolol (0.2 mg/kg; intravenous injection via jugular vein; single administration) significantly reduces pulmonary arterial systolic pressure in mice, but has no effect on systemic arterial systolic pressure^[4].