Synthesis and biological evaluations of a monomethylauristatin E glucuronide prodrug for selective cancer chemotherapy

  • Eur J Med Chem. 2013 Sep:67:75-80. doi: 10.1016/j.ejmech.2013.06.037.
Thibaut Legigan  1 ,  Jonathan Clarhaut ,  Brigitte Renoux ,  Isabelle Tranoy-Opalinski ,  Arnaud Monvoisin ,  Christophe Jayle ,  Jérôme Alsarraf ,  Mikaël Thomas ,  Sébastien Papot
Affiliations
  • 1. Université de Poitiers, UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers (IC2MP), Groupe "Systèmes Moléculaires Programmés", 4 rue Michel Brunet, 86022 Poitiers, France.
PMID: 23845743 DOI: 10.1016/j.ejmech.2013.06.037
Abstract

We developed a glucuronide prodrug of the potent monomethylauristatin E (MMAE). This prodrug is significantly less toxic than the parent drug. However, in the presence of β-glucuronidase the prodrug leads to the efficient release of MMAE thereby triggering a subnanomolar cytotoxic activity against several Cancer cell lines. Preliminary in vivo experiments conducted in C57BL/6 mice bearing a subcutaneous murine Lewis Lung Carcinoma (LLC) demonstrated the potential of this targeting system for the selective treatment of solid tumors.

Keywords
Cancer; Chemotherapy; Glucuronide; Prodrug; Tumor targeting.