This ADC product is comprised of an anti-B. anthracis PA monoclonal antibody conjugated via a SPDB linker to DM4. The DM4 is targeted to certain cancers by immunerecognition and delivered into cancer cells via receptor mediated endocytosis. Within the cell, DM1 binds to tubulins, interrupts microtubule dynamics, and subsequently, induces cell death.
ADC Target
- Alternative Names
- B. anthracis PA
- Overview
- Anthrax toxins are composed of three distinct proteins, a protective antigen (PA), a lethal factor (LF) and an edema factor (EF). None of these proteins are toxic by themselves and several studies indicate that the anthrax toxin has the familiar A-B enzymatic binding structure, with PA acting as the binding domain and EF and/or LF acting as the active fragments.
ADC Antibody
- Overview
- Human Anti-B. anthracis PA IgG1-lambda antibody, Raxibacumab
ADC Linker
- Name
- SPDB (N-succinimidyl-4-(2-pyridyldithio)butyrate)
- Description
- Disulfide Linkers, are extensively exploited as a chemically labile linkage. Since the release of disulfide-linked drugs requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides maintain stable at physiological pH and only when ADCs are internalized inside cells, the cytosol provides reducing environment including intracellular enzyme protein disulfide isomerase, or similar enzymes, drugs can be released.
ADC payload drug
- Name
- DM4 (N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine)
- Description
- Derived from Maytansinoid,a group of cytotoxins structurally similar to rifamycin, geldanamycin, and ansatrienin. The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. Maytansinoids can bind to tubulin at or near the vinblastine-binding site, which interfere the formation of microtubules and depolymerize already formed microtubules, inducing mitotic arrest in the intoxicated cells.
For Research Use Only. NOT FOR CLINICAL USE.
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