product name GKT137831
Description: GKT137831 is a potent, dual NADPH oxidase NOX1/NOX4 inhibitor with Ki of 110 nM and 140 nM, respectively. GKT137831 attenuates hypoxia-induced H(2)O(2) release, cell proliferation, and TGF-β1 expression and blunted reductions in PPARγ 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.
394.85
Formula
C21H19ClN4O2
CAS No.
1218942-37-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 78 mg/mL (197.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GKT137831 attenuates hypoxia-induced H(2)O(2) release, cell proliferation, and TGF-β1 expression and blunted reductions in PPARγ in HPAECs and HPASMCs. GKT137831 also prevents oxidative stress in response to hyperglycemia in human aortic endothelial cells. Kinase Assay: Ki: 140 nM and 110 nM Cell Assay: Hypoxic HPASMC and HPAEC proliferation is determined using MTT assay, by Western blotting to detect proliferating cell nuclear antigen (PCNA) expression, or by manual cell counting after Trypan blue staining. Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit is used to measure H2O2 released into the culture media from HPAECs or HPASMCs. After exposure to control or hypoxic environments for 72 hours, Amplex Red reagent is added, and the cells are returned to control or hypoxic environments for an additional hour before fluorescence measurements. |
|---|---|
| In Vivo | In WT and SOD1mut mice, GKT137831 (60 mg/kg i.g.) blocks liver fibrosis and downregulates markers of oxidative stress, inflammation, and fibrosis. GKT137831 (60 mg/kg/d p.o.) also attenuates chronic hypoxia–induced right ventricular hypertrophy, vascular remodeling, lung cell proliferation, and hypoxic alterations in lung PPARγ and TGF-β1 expression in mouse model of chronic hypoxia exposure. In diabetic apolipoprotein E-deficient mice, GKT137831 (60 mg/kg/d p.o.) attenuates diabetes mellitus-accelerated atherosclerosis. Moreover, in angII-infused c-hNox4Tg mice, GKT137831 abolishes the increase in oxidative stress, suppresses Akt-mTOR and NF-κB signaling pathway and attenuates cardiac remodeling. |
| Animal model | Mouse models of liver fibrosis |
| Formulation & Dosage | Dissolved in corn oil; 60 mg/kg daily; i.p. injection |
| References | Hepatology. 2012 Dec;56(6):2316-27; Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26; Circulation. 2013 May 7;127(18):1888-902. |
