GKT-137831

• CAT Number: I000837
• CAS Number: 1218942-37-0
• Molecular Formula: C₂₁H₂₀ClN₄O₂
• Molecular Weight: 394.85
• Purity: ≥95%
• Target: NADPH Oxidase
• Solubility: DMSO: ≥ 37 mg/mL
• Storage: Store at -20°C
• IC50: 140±40 nM/110±30 nM(Nox1/Nox4, Ki) [1]
• IUPAC Name: 2-(2-chlorophenyl)-4-[3-(dimethylamino)phenyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6-dione
• InChI: InChI=1S/C21H19ClN4O2/c1-24(2)14-8-6-7-13(11-14)20-19-16(12-18(27)25(20)3)23-26(21(19)28)17-10-5-4-9-15(17)22/h4-12,23H,1-3H3
• InChIKey: RGYQPQARIQKJKH-UHFFFAOYSA-N
• SMILES: CN1C(=O)C=C2C(=C1C3=CC(=CC=C3)N(C)C)C(=O)N(N2)C4=CC=CC=C4Cl

Setanaxib（Cat No.:I000837）, also known as GKT137831 or GKT831, is a powerful inhibitor of NADPH oxidase enzymes NOX1 and NOX4. It exhibits Ki values of 110 nM and 140 nM for NOX1 and NOX4, respectively. Treatment with GKT137831 effectively inhibits the production of reactive oxygen species (ROS). Additionally, GKT137831 has shown some ability to inhibit ferroptosis, a form of cell death associated with oxidative stress.

Reference

1:Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease. Gray SP, Jha JC, Kennedy K, van Bommel E, Chew P, Szyndralewiez C, Touyz RM, Schmidt HH, Cooper ME, Jandeleit-Dahm KA.Diabetologia. 2017 May;60(5):927-937. doi: 10.1007/s00125-017-4215-5. Epub 2017 Feb 3. PMID: 28160092 2:Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes. Asensio-López MC, Soler F, Sánchez-Más J, Pascual-Figal D, Fernández-Belda F, Lax A.Arch Biochem Biophys. 2016 Mar 15;594:26-36. doi: 10.1016/j.abb.2016.02.021. Epub 2016 Feb 22. PMID: 26906075 3:The Nox1/4 Dual Inhibitor GKT137831 or Nox4 Knockdown Inhibits Angiotensin-II-Induced Adult Mouse Cardiac Fibroblast Proliferation and Migration. AT1 Physically Associates With Nox4. Somanna NK, Valente AJ, Krenz M, Fay WP, Delafontaine P, Chandrasekar B.J Cell Physiol. 2016 May;231(5):1130-41. doi: 10.1002/jcp.25210. Epub 2015 Oct 19. PMID: 26445208 Free PMC Article4:Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate neuroglial cell inflammation in the retina. Deliyanti D, Wilkinson-Berka JL.J Neuroinflammation. 2015 Jul 30;12:136. doi: 10.1186/s12974-015-0363-z. PMID: 26219952 Free PMC Article5:The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Green DE, Murphy TC, Kang BY, Kleinhenz JM, Szyndralewiez C, Page P, Sutliff RL, Hart CM.Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26. doi: 10.1165/rcmb.2011-0418OC. Epub 2012 Aug 16. PMID: 22904198 Free PMC Article6:Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, Molango S, Heitz F, Merlot C, Szyndralewiez C, Page P, Brenner DA.Hepatology. 2012 Dec;56(6):2316-27. doi: 10.1002/hep.25938. PMID: 22806357 Free PMC Article7:Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Jiang JX, Chen X, Serizawa N, Szyndralewiez C, Page P, Schröder K, Brandes RP, Devaraj S, Török NJ.Free Radic Biol Med. 2012 Jul 15;53(2):289-96. doi: 10.1016/j.freeradbiomed.2012.05.007. Epub 2012 May 19. PMID: 22618020 Free PMC Article