GKT136901 is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with Kis of 160 and 165 nM, respectively. GKT136901 also is a selective and direct scavenger of peroxynitrite. GKT136901 can be used for the research of diabetic nephropathy, stroke, and neurodegeneration. GKT136901 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]. Animal Model: Male db/db and db/m mice (8 weeks)[6]

[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.