5.09306

Late Endosome Trafficking Inhibitor, EGA

• Synonym(s): Late Endosome Trafficking Inhibitor, EGA, 4-Bromobenzaldehyde-N-(2,6-dimethylphenyl)semicarbazone, ( E)-2-(4-Bromobenzylidene)-N-(2,6-dimethylphenyl)hydrazinecarboxamide
• Empirical Formula (Hill Notation): C₁₆H₁₆BrN₃O
• CAS Number: 415687-81-9
• Molecular Weight: 346.22
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥93% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 5 mg/mL
• storage temp.: 2-8°C

Description

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
host-membrane trafficking

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Use only fresh DMSO for reconstitution.

Other Notes

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

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable