title: Synthesis and biological evaluations of a monomethylauristatin E glucuronide prodrug for selective cancer chemotherapy.
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.
authors.affiliation: 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.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Legigan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clarhaut
authors.forename: Brigitte
authors.initials: B
authors.lastname: Renoux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tranoy-Opalinski
authors.forename: Arnaud
authors.initials: A
authors.lastname: Monvoisin
authors.forename: Christophe
authors.initials: C
authors.lastname: Jayle
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alsarraf
authors.forename: Mikaël
authors.initials: M
authors.lastname: Thomas
authors.forename: Sébastien
authors.initials: S
authors.lastname: Papot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D020719:Glucuronides; D009842:Oligopeptides; D011355:Prodrugs; C495575:monomethyl auristatin E
keywords: Cancer; Chemotherapy; Glucuronide; Prodrug; Tumor targeting