| Bioactivity | Setanaxib (GKT137831) is a selective NADPH oxidase (NOX1/4) inhibitor with Kis of 140 and 110 nM, respectively. | ||||||||||||
| Target | Ki: 140±40 nM (Nox1), 1750±700 nM (Nox2), 110±30 nM (Nox4), 410±100 nM(Nox5) | ||||||||||||
| Invitro | Setanaxib (GKT137831) is a potent Nox1/4 inhibitor (Kis=140±40/110±30 nM)[1]. Administration of Setanaxib (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, Setanaxib (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 Setanaxib (GKT137831) attenuates hypoxia-induced pulmonary vascular cell proliferation[2]. | ||||||||||||
| In Vivo | During the last half of CCl4 injections, some mice are treated with Setanaxib (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 Setanaxib (GKT137831) treatment. The increased hepatic α-SMA expression is markedly decreased in SOD1mu mice treated with Setanaxib (GKT137831), to a level similar to that of WT mice given the NOX1/4 inhibitor[1]. | ||||||||||||
| Name | Setanaxib | ||||||||||||
| CAS | 1218942-37-0 | ||||||||||||
| Formula | C21H19ClN4O2 | ||||||||||||
| Molar Mass | 394.85 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Aoyama T, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012 Dec;56(6):2316-27. [2]. Green DE, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26. |