Biological Activity
GKT137831 is a selective NADPH oxidase (NOX1/4) inhibitor with Kis of 140 and 110 nM, respectively.
In Vitro
GKT137831 is a potent Nox4 inhibitor (Ki=120±30 nM) with an affinity similar to the irreversible and unspecific flavoprotein inhibitor Diphenyliodonium (DPI; Ki=70±10 nM)[1]. Administration of GKT137831 throughout the 72-hour period of normoxia or hypoxia exposure attenuates HPASMC proliferation under normoxic conditions at the 20 μM concentration but had no effect on proliferation in normoxic HPAECs. In the prevention paradigm, GKT137831 attenuates hypoxia-induced HPASMC and HPAEC proliferation at 5 and 20 μM. Complementary assays of cell proliferation measuring the expression of PCNA or manual cell counting confirmed that GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation[2].
In Vivo
During the last half of CCl4 injections, some mice are treated with GKT137831 daily. CCl4-induced liver fibrosis is more pronounced in SOD1mu compared to WT mice. Liver fibrosis in both SOD1mu and WT mice is attenuated by GKT137831 treatment. The increased hepatic α-SMA expression is markedly decreased in SOD1mu mice treated with GKT137831, to a level similar to that of WT mice given the NOX1/4 inhibitor[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.