NOX Inhibitor VIII; VAS3947 1PC X 10MG

Biochem/physiol Actions

Primary TargetNADPH Oxidase

Cell permeable: yes

General description

A cell-permeable VAS2870 (Cat No. 492000) analogue that displays improved solubility and effectively blocks ROS production in DMSO-differentiated HL-60 cultures upon oxidative burst induction by PMA (IC₅₀ = 1 µM by Cytochrome C reduction & 2 µM by L012 chemiluminescence; Drug added 30 min prior to 100 nM PMA/500582 & 524400) via NADPH oxidases/NOX inhibition, while displaying no potency against eNOS or xanthine oxidase/XOD enzymatic activity in cell-free assays even at a high concentration of 100 µM. Reported to suppress the high ROS level in isolated thoracis aortas sections from spontaneously hypertensive rats (SHRs) in situ (by 66% with 10 µM) and synergize with Imatinib (Cat. No. 504595) against the proliferation of p210 Bcr-abl-expressing murine Boff 210 cultures. A commonly employed NOX inhibitor Apocynin (Cat. No. 178385), in comparison, is shown to interfere with L012-based assays and exhibit little potency against NOX-mediated ROS production in DMSO-differentiated HL-60 cultures (by Cytochrome C reduction) or in cell-free assays using A7r5 & CaCo-2 homogenates (IC₅₀ >1 mM), while another NOX inhibitor DPI (Cat. No. 300260) is shown to inhibit both eNOS & XOD activities.

A cell-permeable triazolo-pyrimidine derivative of VAS2870 (Cat. No. 492000) that displays enhanced solubility and acts as a selective inhibitor NOX family of NADPH oxidase. Shown to inhibit NOX activity in CaCo-2 cells (expressing NOX 1, 2, 4, and 5; IC₅₀ = 12 µM), HL-60 cells (mainly expressing NOX2; IC₅₀ = 2 µM), and A7r5 cells (mainly expressing NOX3 and 4; IC₅₀ = 13 µM). Does not affect the activities of xanthine oxidase and endothelial nitric oxide synthase (eNOS) even at higher concentrations (~100 µM). Acts synergistically with Imatinib (Cat. No. 504595) to reduce the proliferation of chronic myeloid leukemia (CML) cells.Please note that the molecular weight for this compound is batch-specific due to variable water content.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Sanchez-Sanchez, B., et al. 2014. Clin. Cancer Res.20, 4014.Altenhofer, S., et al., 2012. Cell. Mol. Life Sci.69, 2327.Wind, S., et al. 2010. Br. J. Pharmacol.161, 885.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)