For research use only. Not for therapeutic Use.
GKT136901 hydrochloride is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with Kis of 160 and 165 nM, respectively. GKT136901 hydrochloride is also a selective and direct scavenger of peroxynitrite. GKT136901 hydrochloride can be used for the research of diabetic nephropathy, stroke, and neurodegeneration. GKT136901 hydrochloride also has anti-inflammatory activity[1][2][3].
GKT136901 (10 μM; 30 min) significantly attenuates high-D-glucose-induced increase in O2•− production and in H2O2 generation in MPT cells[4].
GKT136901 (10 μM; 30 min) abolishes the effect of high D-glucose on p38MAP kinase activation in MPT cells[4].
GKT136901 (10 μM; 2 h) attenuates methamphetamine (METH)-induced oxidative stress in HBMECs[5].
GKT136901 (10 μM; 2 h) protects HBMECs against METH-induced blood-brain barrier (BBB) dysfunction[5].
GKT136901 (30-90 mg/kg; daily p.o. for 16 weeks) has renoprotective effects in a mouse model of Type 2 diabetes[6].
| Catalog Number | I045693 |
| CAS Number | 1254507-01-1 |
| Synonyms | 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione;hydrochloride |
| Molecular Formula | C19H16Cl2N4O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C19H15ClN4O2.ClH/c1-12-18-15(10-17(25)23(12)11-13-6-4-5-9-21-13)22-24(19(18)26)16-8-3-2-7-14(16)20;/h2-10,22H,11H2,1H3;1H |
| InChIKey | BIXDBKGUQPCHLH-UHFFFAOYSA-N |
| SMILES | CC1=C2C(=CC(=O)N1CC3=CC=CC=N3)NN(C2=O)C4=CC=CC=C4Cl.Cl |
| Reference | [1]. Laleu B, 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. 2010 Nov 11;53(21):7715-30. [2]. Teixeira G, et, al. Therapeutic potential of NADPH oxidase 1/4 inhibitors. Br J Pharmacol. 2017 Jun;174(12):1647-1669. [3]. Schildknecht S, et, al. The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite. Curr Med Chem. 2014;21(3):365-76. [4]. Sedeek M, et, al. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 2010 Dec;299(6):F1348-58. [5]. Hwang JS, et, al. GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood-brain barrier dysfunction. Life Sci. 2020 Sep 1;256:117917. [6]. Sedeek M, et, al. Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes. Clin Sci (Lond). 2013 Feb;124(3):191-202. |
