Setanaxib (GKT137831) effectively inhibits Nox1/4 (Kis=140±40/110±30 nM)[1]. Setanaxib (GKT137831) administration during a 72-hour normoxia or hypoxia exposure reduces HPASMC proliferation under normoxic conditions at 20 μM but does not affect HPAEC proliferation in normoxia. In prevention studies, Setanaxib (GKT137831) reduces proliferation induced by hypoxia in both HPASMCs and HPAECs at concentrations of 5 and 20 μM. Further tests, including PCNA expression or manual cell counting, confirm that Setanaxib (GKT137831) diminishes hypoxia-induced proliferation in pulmonary vascular cells[2].
体内研究
In the latter phase of CCl4 injections, some mice receive daily doses of Setanaxib (GKT137831). CCl4 causes more severe liver fibrosis in SOD1mu mice than in WT mice. However, Setanaxib (GKT137831) treatment lessens liver fibrosis in both SOD1mu and WT mice. Additionally, the elevated α-SMA expression in the livers of SOD1mu mice treated with Setanaxib (GKT137831) is significantly reduced, aligning with levels seen in WT mice treated with the NOX1/4 inhibitor[1].
Setanaxib (GKT137831) administration during a 72-hour normoxia or hypoxia exposure reduces HPASMC proliferation under normoxic conditions at 20 μM but does not affect HPAEC proliferation in normoxia. In prevention studies, Setanaxib (GKT137831) reduces proliferation induced by hypoxia in both HPASMCs and HPAECs at concentrations of 5 and 20 μM. Further tests, including PCNA expression or manual cell counting, confirm that Setanaxib (GKT137831) diminishes hypoxia-induced proliferation in pulmonary vascular cells[2].
GKT137831 细胞实验
Cell Line
Concentration
Treated Time
Description
References
human podocytes
20 µM
24 h
GKT137831 reduced the high glucose-induced increase in ROS production and apoptosis rate in podocytes.
J Cell Mol Med. 2021 Jan;25(2):1012-1023.
Primary prostate human fibroblasts
30 µM
48 h
GKT137831 significantly attenuated the elevated migratory capacity of activated fibroblasts and reduced CAF marker expression and ROS production.
Int J Cancer. 2018 Jul 15;143(2):383-395.
RAW264.7 macrophages
50 µM
GKT137831 reduced RANKL-induced osteoclastogenesis by inhibiting NOX4 activity without detectable cytotoxicity.
J Nanobiotechnology. 2022 May 23;20(1):241.
CAF5
20 µM
24 h
GKT137831 significantly reduced the ability of CAF5 to contract collagen, promote migration of breast cancer cells, and generate ROS.
Breast Cancer Res. 2022 Jul 14;24(1):48.
Human peritoneal mesothelial cells (HPMCs)
20 µM
2 h
GKT137831 reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage.
Inhibited Dox-induced NLRP3 inflammasome activation and cardiomyocyte pyroptosis
Redox Biol. 2020 Jul;34:101523.
LX-2 human hepatic stellate cells
20 μM
24 h
To evaluate the effect of GKT137831 on Ang II-induced ROS generation and Rac1 activity. Results showed that GKT137831 suppressed ROS generation but did not affect Rac1 activity.
Hepatology. 2012 Dec;56(6):2316-27.
RMF-HGF
30 µM
48 h
GKT137831 significantly inhibited the collagen contractile ability of RMF-HGF and reduced the release of extracellular H2O2.
Breast Cancer Res. 2022 Jul 14;24(1):48.
GKT137831 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CCl4-induced liver fibrosis model
Intragastric injection
60 mg/kg
Once daily for 3 weeks
To evaluate the inhibitory effect of GKT137831 on liver fibrosis. Results showed that GKT137831 significantly reduced liver fibrosis, inflammation, and oxidative stress markers.
Hepatology. 2012 Dec;56(6):2316-27.
Mice
Cisplatin-induced acute kidney injury model
Oral gavage
40mg/kg
Every 12 hours for 3 days
GKT137831 significantly reduced serum creatinine (sCr) and blood urea nitrogen (BUN) levels in FeD mice, indicating that it alleviated cisplatin-induced acute kidney injury by inhibiting Nox4 activity.
Free Radic Biol Med. 2021 Sep;173:81-96
Mice
Db/db diabetic mice
Oral gavage
60 mg/kg
Three times a week for 16 weeks
After 16 weeks of treatment with GKT137831, similar renoprotection as observed in SAL treated db/db mice was achieved, including alleviated mesangial hyperplasia and podocyte foot process effacement in glomeruli.
J Cell Mol Med. 2021 Jan;25(2):1012-1023.
Mice
Liver fibrosis models
Oral
10 mg/kg
Twice weekly
GKT137831 combined with endothelial Hgf gene delivery promoted liver regeneration and reduced fibrosis
Sci Transl Med. 2017 Aug 30;9(405):eaai8710.
C57BL/6 mice
Ti nanoparticle-induced calvarial osteolysis model
Subperiosteal injection
1 mg/kg
Once daily for 14 consecutive days
GKT137831 prevented Ti nanoparticle-induced osteolysis by decreasing ROS levels and osteoclastogenesis through NOX4 inhibition.
J Nanobiotechnology. 2022 May 23;20(1):241.
Mice
4T1 syngeneic model
Oral
60 mg/kg
Daily for 30 days
GKT137831 significantly inhibited the growth of 4T1 mammary tumors and reduced lung metastasis.
Breast Cancer Res. 2022 Jul 14;24(1):48.
C57BL/6J mice
Dox-induced dilated cardiomyopathy model
Gavage
60 mg/kg
Once daily for 6 weeks
Inhibited NOX1 and NOX4 activity, alleviated Dox-induced cardiac dysfunction and myocardial damage
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