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

2013; Elsevier BV; Volume: 67; Linguagem: Inglês

10.1016/j.ejmech.2013.06.037

1768-3254

Thibaut Legigan, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy‐Opalinski, Arnaud Monvoisin, Christophe Jayle, Jérôme Alsarraf, Mikaël Thomas, Sébastien Papot,

Proteoglycans and glycosaminoglycans research

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.