| Identification | Back Directory | [Name]
2-(2-chlorophenyl)-4-Methyl-5-(pyridin-2-ylMethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione | [CAS]
955272-06-7 | [Synonyms]
AK120765
GKT136901
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione
2-(2-chlorophenyl)-4-Methyl-5-(pyridin-2-ylMethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
1H-Pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione, 2-(2-chlorophenyl)-4-methyl-5-(2-pyridinylmethyl)- | [Molecular Formula]
C19H15ClN4O2 | [MDL Number]
MFCD09961532 | [MOL File]
955272-06-7.mol | [Molecular Weight]
366.8 |
| Chemical Properties | Back Directory | [Boiling point ]
530.2±60.0 °C(Predicted) | [density ]
1.48±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMF:25.0(Max Conc. mg/mL);68.16(Max Conc. mM)
DMSO:30.0(Max Conc. mg/mL);81.79(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:6):0.14(Max Conc. mg/mL);0.38(Max Conc. mM)
Ethanol:1.0(Max Conc. mg/mL);2.73(Max Conc. mM) | [form ]
A solid | [pka]
4.22±0.12(Predicted) | [color ]
Off-white to light brown |
| Hazard Information | Back Directory | [Uses]
GKT136901 is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with Kis of 160 and 165 nM, respectively. GKT136901 is also 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]. | [Biological Activity]
Cell permeable: yes''Primary Target
NOX1- and NOX4-containing NADPH oxidase activity''Reversible: yes | [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.
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| [IC 50]
NOX1; NOX4 | [storage]
Store at -20°C | [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. DOI:10.1021/jm100773e
[2] Teixeira G, et, al. Therapeutic potential of NADPH oxidase 1/4 inhibitors. Br J Pharmacol. 2017 Jun;174(12):1647-1669. DOI:10.1111/bph.13532
[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. DOI:10.2174/09298673113209990179
[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. DOI:10.1152/ajprenal.00028.2010
[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. DOI:10.1016/j.lfs.2020.117917
[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. DOI:10.1042/CS20120330 |
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