A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions

Chem Commun (Camb). 2011 Oct 14;47(38):10752-4. doi: 10.1039/c1cc14164c. Epub 2011 Aug 26.

Abstract

A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 °C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells.

MeSH terms

  • Antibodies / chemistry*
  • Cell Line, Tumor
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoconjugates / blood
  • Immunoconjugates / chemistry*
  • Immunoconjugates / toxicity
  • Maleimides / chemistry
  • Maytansine / chemistry*
  • Oxidation-Reduction
  • Polyethylene Glycols / chemistry
  • Sulfenic Acids / chemistry

Substances

  • Antibodies
  • Immunoconjugates
  • Maleimides
  • Sulfenic Acids
  • Maytansine
  • Polyethylene Glycols
  • N-(4-carboxycyclohexylmethyl)maleimide N-hydroxysuccinimide ester