GKT137831

GKT137831 is a dual inhibitor of both NOX1 and NOX4 with K_i values in the range of 100 to 150 nM in cell-free assays of ROS production.¹ It shows only weak inhibitory activity against NOX2 or xanthine oxidase and does not block neutrophil oxidative burst, scavenge ROS, or have antioxidant activity.^1,2 GKT137831 displays good oral bioavailability with high plasma concentrations in vivo and attenuates liver fibrosis in mice.^1,2,3 It reduces hypoxia-induced pulmonary vascular cell proliferation, ameliorates dopaminergic neuronal death, and provides renoprotection in long-term diabetic nephropathy.^4,5,6

WARNING This product is not for human or veterinary use.

1. Jiang, J.X., Chen, X., Serizawa, N., et al. Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic. Biol. Med. 53(2), 289-296 (2012).

2. Laleu, B., Gaggini, F., Orchard, M., et al. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J. Med. Chem. 53(21), 7715-7730 (2010).

3. Aoyama, T., Paik, Y.H., Watanabe, S., et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56(6), 2316-2327 (2012).

4. Green, D.E., Murphy, T.C., Kang, B.Y., et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am. J. Respir. Cell Mol. Biol. 47(5), 718-726 (2012).

5. Choi, D.H., Kim, J.H., Seo, J.H., et al. Matrix metalloproteinase-3 causes dopaminergic neuronal death through Nox1-regenerated oxidative stress. PLoS One 9(12), (2014).

6. Jha, J.C., Gray, S.P., Barit, D., et al. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J. Am. Soc. Nephrol. 25(6), 1237-1254 (2014).

Vendrov, A.E., Xiao, H., Lozhkin, A., et al. Cardiomyocyte NOX4 regulates resident macrophage-mediated inflammation and diastolic dysfunction in stress cardiomyopathy. Redox Biol. 67:102937, (2023).

Soriano-Castell, D., Currais, A., and Maher, P. Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis. Free Radic. Biol. Med. S0891-5849(21), (2021).