Biochem/physiol Actions

Primary TargetIκBαee ubiquitination

Target IC₅₀: 2.3 µM against IκBαee ubiquitination

Reversible: no

Product does not compete with ATP.

Cell permeable: yes

General description

A cell-permeable tetrazolopyridazine-phenylsulfoxide compound that displays anti-inflammatory properties. Acts as a highly selective, irreversible inhibitor of IκBAee ubiquitination (IC₅₀ = 2.3 µM). Also reported to prevent degradation of IκBAee in MM6 cells (complete inhibition at ~3-5 µM). Shown to block NF-κB-dependent cytokine expression in human peripheral blood mononuclear cells (PBMN) (IC₅₀ = 600-700 nM for TNF-A, IL-1β, and IL-6 inhibition). Also shown to lower circulating levels of TNFA in LPS-treated rats. Also shown to inhibit 5-lipoxygenase (89% inhibition) and EGFR kinase (63% inhibition) at higher concentrations (10 µM).

A cell-permeable tetrazolopyridazine-phenylsulfoxide compound that displays anti-inflammatory properties. Acts as a highly selective, irreversible inhibitor of IκBAee ubiquitination (IC₅₀ = 2.3 µM). Blocks NF-κB-dependent cytokine expression in human PBMNs (IC₅₀’s = ~ 700 nM for TNF-A, IL-1β, and IL-6 inhibition) and rats. Does not inhibit SCF^βTRCP(IκBα ubiquitin ligase)-mediated β-catenin ubiquitination in Jurkat cells. At 10 µM concentrations, also inhibits the activities of 5-lipoxygenase (by 89%) and EGFR kinase (by 63%).

Legal Information

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

Other Notes

Swinney, D.C., et al. 2002. J. Biol. Chem.277, 23573.

Packaging

1 mg in Plastic ampoule

Packaged under inert gas

Reconstitution

Following reconstitution, aliquot and freeze (-70°C). Stock solutions are stable for up to 3 months at -70°C.

Warning

Toxicity: Standard Handling (A)