GKT137831 attenuated hypoxia-induced H(2)O(2) release, proliferation, and TGF-β1 expression and blunted reductions in PPARγ in HPAECs and HPASMCs in vitro. In vivo GKT137831 inhibited hypoxia-induced increases in TGF-β1 and reductions in PPARγ expression and attenuated RVH and pulmonary artery wall thickness but not increases in RVSP or muscularization of small arterioles.Targeting Nox4 with GKT137831 provides a novel strategy to attenuate hypoxia-induced alterations in pulmonary vascular wall cells that contribute to vascular remodeling and RVH, key features involved in PH pathogenesis.GKT137831, attenuated liver fibrosis and ROS production in both SOD1mu and WT mice as well as messenger RNA expression of fibrotic and NOX genes.Treatment with GKT137831 suppressed ROS production and NOX and fibrotic gene expression, but not Rac1 activity, in SOD1mut and WT HSCs. Both Ang II and tumor growth factor beta up-regulated NOX4, but Ang II required NOX1.GKT137831 is a potent inhibitor of fibrosis and hepatocyte apoptosis; therefore, it is a promising therapeutic agent for future translational studies.
FASEB J. 2021 Apr;35(4):e21531.
Inhibition of NADPH oxidase 4 attenuates lymphangiogenesis and tumor metastasis in breast cancer
GKT137831 purchased from AbMole
|Source||Cell Physiol Biochem (2018). Figure 5. GKT137831|
|Cell Lines||AML12 cells|
|Concentrations||0.2, 1 and 5 μM|
|Incubation Time||1 h|
|Results||Importantly, the application of GKT137381 dose-dependently decreased the percentage of PA-induced apoptosis in cultured AML12 cells|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO 10 mg/mL|
The Nox4 inhibitor GKT137831 attenuates hypoxia-induced pulmonary vascular cell proliferation.
Green DE, et al. Am J Respir Cell Mol Biol. 2012 Nov;47(5):718-26. PMID: 22904198.
Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent.
Aoyama T, et al. Hepatology. 2012 Dec;56(6):2316-27. PMID: 22806357.
Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo.
Jiang JX, et al. Free Radic Biol Med. 2012 Jul 15;53(2):289-96. PMID: 22618020.
Forodesine hydrochloride is a potent and orally active transition-state analog inhibitor of purine nucleoside phosphorylase, with IC50 values ranging from 0.48 to 1.57 nM for human, mouse, rat, monkey and dog PNP.
Esaxerenone (CS-3150) is a highly potent and selective non-steroidal mineralocorticoid receptor antagonist.
EC5026 (BPN-19186) is a first-in-class, potent and orally active soluble inhibitor of Epoxide Hydrolase (sEH). EC5026 has the potential to relieve pain by stabilizing natural analgesic and anti-inflammatory mediators.
VPC-80051 is a novel inhibitor of hnRNP A1 that targets the hnRNP A1 RBD.
|D-Ribose 5-phosphate disodium
D-Ribose 5-phosphate disodium is an intermediate of the oxidative branch of the pentose phosphate pathway (PPP) and an end product of the nonoxidative branch of the PPP.
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