Size | Price | Stock | Qty |
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5mg |
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10mg |
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50mg |
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100mg |
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Other Sizes |
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Targets |
NOX1 NOX4
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ln Vitro |
The increase in O2 caused by high d-glucose is significantly reduced by GKT136901 hydrochloride (10 μM; 30 min).- generation as well as H2O2 generation in MPT cells [4]. In MPT cells, the effects of high D-glucose on p38MAP kinase activation are eliminated by GKT136901 hydrochloride (10 μM; 30 min) [4]. In HBMEC, GKT136901 hydrochloride (10 μM; 2 hours) reduces oxidative stress caused by methamphetamine (METH) [5]. HBMEC is protected from METH-induced blood-brain barrier (BBB) dysfunction by GKT136901 hydrochloride (10 μM; 2 hours) [5].
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ln Vivo |
In a mouse model of type 2 diabetes, GKT136901 hydrochloride (30-90 mg/kg; administered orally daily for 16 weeks) has renoprotective properties[6].
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Animal Protocol |
Animal/Disease Models: Male db/db and db/m mice (8 weeks)[6]
Doses: 30, 90 mg/kg Route of Administration: Daily po for 16 weeks Experimental Results: decreased 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. |
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. |
Molecular Formula |
C19H16CL2N4O2
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Molecular Weight |
403.26
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CAS # |
1254507-01-1
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Related CAS # |
GKT136901;955272-06-7
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SMILES |
ClC1=C([H])C([H])=C([H])C([H])=C1N1C(C2([H])C([H])(C([H])([H])[H])N(C([H])([H])C3=C([H])C([H])=C([H])C([H])=N3)C(C([H])([H])C2([H])N1[H])=O)=O.Cl[H]
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: 62.5 mg/mL (154.99 mM)
H2O: 4 mg/mL (9.92 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4798 mL | 12.3989 mL | 24.7979 mL | |
5 mM | 0.4960 mL | 2.4798 mL | 4.9596 mL | |
10 mM | 0.2480 mL | 1.2399 mL | 2.4798 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.