setanaxib-gkt137831

Description: Setanaxib (also known as GKT-137831; GTK831) is a novel, specific, potent, orally bioavailable, and dual inhibitor of NADPH oxidase NOX1/NOX4 with Ki of 110 nM and 140 nM, respectively. It was discovered by rational drug design following a campaign of high-throughput screening on several NOX isoforms. Initially, GKT137831 was developed to treat Idiopathic pulmonary fibrosis and obtained orphan drug designation from both FDA and EMEA in 2010. GKT137831 attenuates hypoxia-induced H2O2 release, cell proliferation, and TGF-beta1 expression and blunted reductions in PPARgamma in HPAECs and HPASMCs. GKT137831 also prevents oxidative stress in response to hyperglycemia in human aortic endothelial cells. In WT and SOD1mut mice, GKT137831 (60 mg/kg i.g.) prevents liver fibrosis and downregulates markers of oxidative stress, inflammation, and fibrosis.

References: Hepatology. 2012 Dec; 56(6):2316-27; Am J Respir Cell Mol Biol. 2012 Nov; 47(5):718-26.

Exact Mass: 394.11965

Chemical Name: 2-(2-chlorophenyl)-4-(3-(dimethylamino)phenyl)-5-methyl-1, 2-dihydro-3H-pyrazolo[4, 3-c]pyridine-3, 6(5H)-dione

SMILES Code: CN(C)C1=CC(C2=C(C(N(C3=CC=CC=C3Cl)N4)=O)C4=CC(N2C)=O)=CC=C1