| Description | GKT136901 hydrochloride is a powerful, selective, and orally active inhibitor of NADPH oxidase (NOX1/4). It exhibits K i values of 160 nM and 165 nM against NOX1 and NOX4, respectively. Additionally, GKT136901 hydrochloride demonstrates selectivity and direct scavenging ability towards peroxynitrite. This compound finds utility in studying diabetic nephropathy, stroke, neurodegeneration, and possesses anti-inflammatory properties. |
| In vitro | GKT136901 (10 μM; 30 min) significantly attenuates high-D-glucose-induced increase in O 2 ?? production and in H 2 O 2 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]. |
| In vivo | 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]Dosage: 30, 90 mg/kg Administration: Daily p.o. for 16 weeks Result: Reduced albuminuria, thiobarbituric acid-reacting substances (TBARS) and renal ERK1/2 phosphorylation and preserved renal structure in diabetic mice. Had no effect on plasma glucose, BP (blood pressure), and body weight. |
| Synonyms | GKT136901 hydrochloride |
| molecular weight | 403.26 |
| Molecular formula | C19H16Cl2N4O2 |
| CAS | 1254507-01-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| References | 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. |