NRF2 ACTIVATOR IV VSC2 (C15-1305-012)

General description

A cell-permeable vinylsulfone compound that acts as a more potent Nrf-2 activator than the analogous α,β-unsaturated ketone-based chalcones (e.g. Cat. No. 492040) in stimulating HO-1 expression in murine microglial BV-2 cultures (382% of control protein level in 24 h; 20 µM). Drug treatment in murine dopaminergic (DAergic) CATH.a cultures likewise effectively induces Nrf2 nuclear translocation (Fold of control in 3 h/dose = 1.4/1 µM, 2.3/5 µM, 3.4/10 µM) and overall Nrf2 cellular accumulation (Fold of control in 24 h/dose = 1.5/0.5 µM, 2.0/1 µM, 2.8/2 µM, 4.3/5 µM), presumably by freeing Nrf2 from its negative regulator keap1, with concomitant upregulation of Nrf2-regulated antioxidant enzymes expression, including heme oxygenase-1/OH-1, NAD(P)H quinone oxidoreductase 1/NQO1, glutamate-cysteine ligase modifier & catalytic subunits, QCLM & GCLC. Shown to protect CATH.a against BH4 toxicity (effective conc. 0.1 to 1.0 µM against 200 µM BH4 for 24 h) in vitro and prevent MPTP- (Cat. No. 506382) induced motor deficits/dysfunctions (by vertical grid test 6 d post MPTP injection) and neurodegeneration (by TH staining 7 d post MPTP injection) in a murine PD model in vivo (3 X 10 mg drug/kg/d oral dosages; 4X 20 mg MPTP/kg/2 h i.p. dosages starting 24 h post the 1st drug dosage).

A cell-permeable vinylsulfone that acts as a more potent Nrf-2 activator than the chalcones (e.g. Cat. No. 492040) in stimulating HO-1 expression in murine microglial BV-2 cultures (3.82-fold of control in 24 h; 20 µM). Shown to induce overall Nrf2 cellular accumulation & nuclear translocation (1 to10 µM) in murine dopaminergic CATH.a cultures, presumably by freeing Nrf2 from its negative regulator keap1, with concomitant upregulation of Nrf2-regulated antioxidant enzymes expression, effectively protecting CATH.a against BH4 toxicity (effective conc. 0.1 to 1.0 µM against 200 µM BH4; 24 h) in vitro and preventing MPTP- (Cat. No. 506382) induced motor dysfunctions and neurodegeneration in a murine PD model in vivo (3X 10 mg drug/kg/d p.o.; 4X 20 mg MPTP/kg/2 h i.p.).

Biochem/physiol Actions

Cell permeable: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Other Notes

Lee, J.A., et al. 2015. Br. J. Pharmacol.172, 1087.
Woo, S.Y., et al. 2014. J. Med. Chem.57, 1473.

Legal Information

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

Molecular Weight: 308.78. Empirical Formula: C₁₅H₁₃ClO₃S. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: off-white. solubility: DMSO: 100 . 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.