NOX INHIBITOR VIII VAS3947 (C15-1305-074)

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
NADPH Oxidase

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

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.

Legal Information

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

Molecular Weight: 310.33. Empirical Formula: C₁₄H₁₀N₆OS. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: light yellow. solubility: DMSO: 50 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.