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Purity: ≥98%
Setanaxib (also known as GKT-137831; GTK831) is a novel, specific, potent, orally bioavailable, and dual inhibitor of NADPH oxidase NOX1/NOX4 with Ki of 110 nM and 140 nM, respectively. It was discovered by rational drug design following a campaign of high-throughput screening on several NOX isoforms. Initially, GKT137831 was developed to treat Idiopathic pulmonary fibrosis and obtained orphan drug designation from both FDA and EMEA in 2010. GKT137831 attenuates hypoxia-induced H2O2 release, cell proliferation, and TGF-β1 expression and blunted reductions in PPARγ in HPAECs and HPASMCs. GKT137831 also prevents oxidative stress in response to hyperglycemia in human aortic endothelial cells. In WT and SOD1mut mice, GKT137831 (60 mg/kg i.g.) prevents liver fibrosis and downregulates markers of oxidative stress, inflammation, and fibrosis.
| ln Vitro |
A strong Nox1/4 inhibitor, setanaxib (GKT137831) with a Kis of 140±40/110±30 nM[1]. Setanaxib (GKT137831) administration attenuates HPASMC proliferation under normoxic conditions at the 20 μM concentration during the 72-hour exposure to hypoxia or normoxia, but has no effect on proliferation in normoxic HPAECs. Setanaxib (GKT137831) inhibits the growth of HPASMC and HPAEC caused by hypoxia at concentrations of 5 and 20 μM in the preventive paradigm. The pulmonary vascular cell proliferation induced by hypoxia is inhibited by Setanaxib (GKT137831), according to complementary assays detecting PCNA expression or manual cell counting[2].
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| ln Vivo |
For the latter half of their CCl4 injections, some mice receive daily treatments of Setanaxib (GKT137831). Compared to WT mice, SOD1mu exhibit more severe hepatic fibrosis as a result of CCl4 exposure. Treating SOD1mu and WT mice with Setanaxib (GKT137831) reduces liver fibrosis. Setanaxib (GKT37831) treatment significantly reduces the elevated hepatic α-SMA expression in SOD1mu mice, bringing it down to a level comparable to WT animals given the NOX1/4 inhibitor[1].
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| References |
[1]. Aoyama T, et al. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology. 2012 Dec;56(6):2316-27.
[2]. Green DE, et al. The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26 |
| Molecular Formula |
C21H19CLN4O2
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| Molecular Weight |
394.85
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| CAS # |
1218942-37-0
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| Related CAS # |
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| SMILES |
CN(C)C1=CC(C2=C(C(N(C3=CC=CC=C3Cl)N4)=O)C4=CC(N2C)=O)=CC=C1
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| Chemical Name |
2-(2-chlorophenyl)-4-(3-(dimethylamino)phenyl)-5-methyl-1,2-dihydro-3H-pyrazolo[4,3-c]pyridine-3,6(5H)-dione
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| Synonyms |
GTK831; GTK-831; GKT-137831; GKT137831; GKT 137831; GTK 831.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.33 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.33 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. View More
Solubility in Formulation 3: ≥ 1.43 mg/mL (3.62 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5326 mL | 12.6630 mL | 25.3261 mL | |
| 5 mM | 0.5065 mL | 2.5326 mL | 5.0652 mL | |
| 10 mM | 0.2533 mL | 1.2663 mL | 2.5326 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.
 Enhanced liver fibrosis in SOD1mu mice is suppressed by inhibition of NOX1/4 with GKT137831.Hepatology.2012 Dec;56(6):2316-27. |
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 Pharmacological profile of GKT137831, a dual Nox1/Nox4 inhibitor.Hepatology.2012 Dec;56(6):2316-27. |
 Enhanced liver inflammation in SOD1mu mice is suppressed by NOX1/4 inhibition.Hepatology.2012 Dec;56(6):2316-27. |
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