Setanaxib (GKT137831)

Catalog No.S7171 Batch:S717107

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Technical Data

Formula

C21H19ClN4O2
Molecular Weight 394.85 CAS No. 1218942-37-0
Solubility (25°C)* In vitro DMSO 78 mg/mL (197.54 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Setanaxib (GKT137831, GKT831) is a potent, dual NADPH oxidase NOX1/NOX4 inhibitor with Ki of 110 nM and 140 nM, respectively. Treatment with GKT137831 suppresses reactive oxygen species (ROS) production. GKT137831 partly inhibits ferroptosis.
Targets
Ferroptosis [5] NOX1 [1]
(Cell-based assay)		 NOX4 [1]
(Cell-based assay)
110 nM(Ki) 140 nM(Ki)
In vitro

GKT137831 attenuates hypoxia-induced H(2)O(2) release, cell proliferation, and TGF-β1 expression and blunted reductions in PPARγ in HPAECs and HPASMCs. [2] GKT137831 also prevents oxidative stress in response to hyperglycemia in human aortic endothelial cells. [3]
In vivo

In WT and SOD1mut mice, GKT137831 (60 mg/kg i.g.) blocks liver fibrosis and downregulates markers of oxidative stress, inflammation, and fibrosis. [1] GKT137831 (60 mg/kg/d p.o.) also attenuates chronic hypoxia–induced right ventricular hypertrophy, vascular remodeling, lung cell proliferation, and hypoxic alterations in lung PPARγ and TGF-β1 expression in mouse model of chronic hypoxia exposure. [2] In diabetic apolipoprotein E-deficient mice, GKT137831 (60 mg/kg/d p.o.) attenuates diabetes mellitus-accelerated atherosclerosis. [3] Moreover, in angII-infused c-hNox4Tg mice, GKT137831 abolishes the increase in oxidative stress, suppresses Akt-mTOR and NF-κB signaling pathway and attenuates cardiac remodeling. [4]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    Hypoxic HPASMC and HPAECs

  • Concentrations

    20 μM

  • Incubation Time

    72 hours

  • Method

    Hypoxic HPASMC and HPAEC proliferation is determined using MTT assay, by Western blotting to detect proliferating cell nuclear antigen (PCNA) expression, or by manual cell counting after Trypan blue staining. Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit is used to measure H2O2 released into the culture media from HPAECs or HPASMCs. After exposure to control or hypoxic environments for 72 hours, Amplex Red reagent is added, and the cells are returned to control or hypoxic environments for an additional hour before fluorescence measurements.
Animal Study:

[1]
  • Animal Models

    Mouse models of liver fibrosis

  • Dosages

    60 mg/kg daily

  • Administration

    i.g.

Customer Product Validation

, , Mol Med, 2016, doi: 10.2119/molmed.2015.00250

Data from [Data independently produced by , , Biochim Biophys Acta, 2016, 1861(1 Pt A):2912-2921. ]

Data from [Data independently produced by , , Exp Cell Res, 2017, 352(2):245-254]

Data from [Data independently produced by , , Int J Mol Sci, 2016, 17(9). pii: E1567]

Selleck's Setanaxib (GKT137831) has been cited by 71 publications

trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing [ Immunity, 2024, 57(1):52-67.e10] PubMed: 38091995
Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion [ Nat Commun, 2024, 15(1):8663] PubMed: 39375351
Autophagy-mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization [ MedComm (2020), 2024, 5(8):e668] PubMed: 39081514
Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells [ Biomed Pharmacother, 2024, 170:116042] PubMed: 38118351
Sevoflurane Exposure Induces Neuronal Cell Ferroptosis Initiated by Increase of Intracellular Hydrogen Peroxide in the Developing Brain via ER Stress ATF3 Activation [ Mol Neurobiol, 2024, 61(4):2313-2335] PubMed: 37874483
Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice [ Nat Commun, 2023, 14(1):1235] PubMed: 36871047
NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation [ Theranostics, 2023, 13(9):2863-2878] PubMed: 37284448
NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation [ Theranostics, 2023, 13(9):2863-2878] PubMed: 37284448
The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage [ Cell Death Dis, 2023, 14(12):825] PubMed: 38092733
Adipocyte-Derived Exosomal NOX4-Mediated Oxidative Damage Induces Premature Placental Senescence in Obese Pregnancy [ Int J Nanomedicine, 2023, 18:4705-4726] PubMed: 37608820

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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