Anti-ERBB2 (Trastuzumab)-SPDB-DM4 ADC (ADC-W-2595)

 ADC Target

  • Name
  • ERBB2
  • Alternative Names
  • ERBB2; v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian); NGL, v erb b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog); receptor tyrosine-protein kinase erbB-2; CD340; HER 2; HER2; NEU; herstatin; p185erbB2; proto-oncogene Neu; c-erb B2/neu protein; proto-oncogene c-ErbB-2; metastatic lymph node gene 19 protein; tyrosine kinase-type cell surface receptor HER2; neuroblastoma/glioblastoma derived oncogene homolog; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog); NGL; TKR1; HER-2; MLN 19; HER-2/neu;
  • Target Entrez Gene ID
  • 2064
  • Overview
  • This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.

 ADC Antibody

  • Overview
  • Humanized Anti-ERBB2 IgG1-kappa antibody, Trastuzumab
  • Generic name
  • Trastuzumab
  • Host animal
  • Mouse

 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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