The first generation of β-galactosidase-responsive prodrugs designed for the selective treatment of solid tumors in prodrug monotherapy

Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11606-10. doi: 10.1002/anie.201204935. Epub 2012 Sep 20.

Abstract

Massive attack: Galactoside prodrugs have been designed that can be selectively activated by lysosomal β-galactosidase located inside cancer cells expressing a specific tumor-associated receptor. This efficient enzymatic process triggers a potent cytotoxic effect, releasing the potent antimitotic agent MMAE and allowing the destruction of both receptor-positive and surrounding receptor-negative tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobenzoates / administration & dosage
  • Aminobenzoates / chemistry
  • Aminobenzoates / metabolism
  • Aminobenzoates / therapeutic use*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Delivery Systems
  • Humans
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Oligopeptides / administration & dosage
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / therapeutic use*
  • Prodrugs / administration & dosage
  • Prodrugs / chemistry
  • Prodrugs / metabolism
  • Prodrugs / therapeutic use*
  • beta-Galactosidase / metabolism*

Substances

  • Aminobenzoates
  • Antineoplastic Agents
  • Oligopeptides
  • Prodrugs
  • auristatin
  • beta-Galactosidase