A dual inhibitor of NOX1 and NOX4
GKT136901 is a dual inhibitor of NADPH oxidase 1 (NOX1) and NOX4 (Kis = 160 and 165 nM, respectively).1 It is selective for NOX1 and NOX4 over NOX2 and xanthine oxidase (Kis = 1,530 and >30,000 nM, respectively), as well as over a panel of 18 enzymes and ion channels at 10 ?M. GKT136901 (0.1, 1, and 10 ?M) scavenges peroxynitrite radicals, as well as prevents the nitration and dimerization of α-synuclein, in cell-free assays.2 It prevents peroxynitrite-induced cell death of differentiated LUHMES cells when used at a concentration of 10 ?M.
1.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 fibrosisJ. Med. Chem.53(21)7715-7730(2010) 2.Schildknecht, S., Weber, A., Gerding, H.R., et al.The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitriteCurr. Med. Chem.21(3)365-376(2014)
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