Anti-IL12+IL23 (Briakinumab)-SPDB-DM4 ADC (ADC-W-2025)

 ADC Target

  • Name
  • IL12+IL23
  • Alternative Names
  • IL12+IL23
  • Overview
  • Interleukin-12 (IL-12; one of the most important T helper 1 (Th1) cytokines) is a component of the complex signal network between lymphoid and neoplastic cells. Systemic or local administration of IL-12 upregulates vascular endothelial adhesion molecule-1 on the endothelial surface, recruits leukocytes to the tumor site, and leads to ischemic–hemorrhagic necrosis of the tumor. IL-12 also inhibits tumor angiogenesis. Interleukin-23 (IL-23) is a heterodimeric cytokine composed of an IL12B (IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit. A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.

 ADC Antibody

  • Overview
  • Human Anti-IL12+IL23 IgG1-lambda antibody, Briakinumab
  • Generic name
  • Briakinumab
  • Host animal
  • Human

 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.

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