Anti-MET (Onartuzumab)-SPDB-DM4 ADC (ADC-W-1539)

This ADC product is comprised of an anti-MET monovalent 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

  • Name
  • MET
  • Alternative Names
  • MET; met proto-oncogene (hepatocyte growth factor receptor); hepatocyte growth factor receptor; HGFR; RCCP2; SF receptor; HGF receptor; oncogene MET; HGF/SF receptor; proto-oncogene c-Met; scatter factor receptor; tyrosine-protein kinase Met; met proto-oncogene tyrosine kinase; AUTS9; c-Met;
  • Target Entrez Gene ID
  • 4233
  • Overview
  • This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers.

 ADC Antibody

  • Overview
  • Humanized Anti-MET IgG1 monovalent antibody, Onartuzumab
  • Generic name
  • Onartuzumab
  • 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.

For Research Use Only. NOT FOR CLINICAL USE.


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