GKT-137831

SKU: orb1301074

Description

Setanaxib (GKT137831) is a selective dual inhibitor targeting the NADPH oxidase isoforms NOX1 and NOX4. It is widely used in research to investigate the role of oxidative stress in fibrotic diseases, cancer, and diabetic nephropathy, with applications in both in vitro and in vivo experimental models.

Research Area

Immunology & Inflammation, Neuroscience

Key Properties

• CAS Number: 1218942-37-0
• MW: 394.85
• Purity: >98%
• Formula: C₂₁H₁₉ClN₄O₂
• SMILES: CN(C)c1cccc(c1)-c1n(C)c(=O)cc2[nH]n(-c3ccccc3Cl)c(=O)c12
• Target: Nox (NADH/NADPH oxidase)
• Solubility: Soluble in DMSO (up to 65 mg/ml)

Bioactivity

• Target IC50:
  NOX4:140 nM(Ki)|NOX1:110 nM(Ki)
• In Vivo:
  GKT137831 can prevent oxidative stress in human aortic endothelial cells in response to hyperglycemia. It attenuates the release of H2O2, cellular proliferation, and TGF-β1 expression induced by hypoxia in HPAECs and HPASMCs, while also ameliorating the reduction in PPARγ expression.
• In Vitro:
  Administering 60 mg/kg of GKT137831 orally every day to mice models living in a chronic hypoxic environment mitigates long-term hypoxia-induced right ventricular hypertrophy, vascular remodeling, pulmonary cell proliferation, and alters the expression of pulmonary PPARγ and TGF-β. Similarly, daily oral administration of 60 mg/kg GKT137831 to atherosclerotic mice deficient in apolipoprotein E (ApoE) under diabetic conditions attenuates accelerated arteriosclerosis. Additionally, GKT137831 at a dosage of 60 mg/kg i.g. blocks the progression of liver fibrosis in both WT and SOD1mut mice, and reduces oxidative stress, inflammation, and fibrogenesis. Furthermore, in AngII-infused c-hNox4Tg mice, GKT137831 eradicates the increase in oxidative stress, inhibits the Akt-mTOR and NF-κB signaling pathways, and diminishes cardiac remodeling.
• Cell Research:
  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 Water2 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. (Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Setanaxib; GKT-831

Compound Identifiers

PubChem CID

58496428