Biochem/physiol Actions

Primary Targethost-membrane trafficking

Reversible: yes

Cell permeable: yes

General description

A cell-permeable semicabazone compound that prevents B. anthrax Lethal toxin/LT (EC₅₀ = 1.7 µM in RAW264.7 cultures; EC_max = 6 µM in murine BMDM cultures), diphtheria toxin/DT, P. aeruginosa ExoA, and H. ducreyi cytolethal distending toxin (Hd-CDT) from exerting their cytotoxic activity, but not endocytic uptake, by blocking endosomal trafficking/maturation into acidified late endosomes, while exhibiting no cytoprotective efficacy against ricin & E. coli Ec-CDT that do not require acidified endosomes for intoxication. Likewise, EGA is also shown to inhibit low-pH-dependent viral infectivity by Armstrong strain of LCMV, A/WSN/33 strain of influenza virus, but not low-pH-independent infection of Nipah virus NiV or MLV. Although the exact molecular target remains unknown, EGA does not act as a pH neutralizing agent, nor does it inhibit endosomal recycling or trafficking to phagocytic compartments.

A cell-permeable semicarbazone compound that prevents B. anthrax Lethal toxin/LT (Protective Antigen/PA & LF/Lethal Factor complex; EC₅₀ = 1.7 µM in RAW264.7 cultures; EC_max = 6 µM in murine BMDM cultures), diphtheria toxin (DT), LF-DT A chain fusion LFnDTA/PA complex, P. aeruginosa ExoA, and H. ducreyi cytolethal distending toxin (Hd-CDT) from exerting their cytotoxic activity, but not endocytic uptake, by blocking endosomal trafficking/maturation into acidified late endosomes, while exhibiting no cytoprotective efficacy against toxins that do not require acidified endosomes for intoxication, such as ricin & E. coli Ec-CDT. Likewise, EGA is also shown to inhibit low-pH-dependent viral infectivity by Armstrong strain of LCMV, A/WSN/33 strain of influenza virus, vesicular stomatitis virus VSV-pseudotyped lentivirus & VSV-pseudotyped MLV, but not low-pH-independent infection of Nipah virus NiV or MLV. Although the exact molecular target remains unknown, EGA does not act as a pH neutralizing agent, nor does it inhibit endosomal recycling or trafficking to phagocytic compartments.

Legal Information

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

Other Notes

Gillespie, E.J., et al. 2013. Proc. Natl. Acad. Sci. USA110, E4904.

Packaging

25 mg in Glass bottle

Packaged under inert gas

Reconstitution

Use only fresh DMSO for reconstitution.

Warning

Toxicity: Standard Handling (A)