title: A new cyclopamine glucuronide prodrug with improved kinetics of drug release.
abstract: We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of β-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity.
authors: Université de Poitiers, UMR-CNRS 6514, 4 rue Michel Brunet, BP 633, 86022, Poitiers, France.
authors: Brigitte
authors: B
authors: Renoux
authors: Thibaut
authors: T
authors: Legigan
authors: Souheyla
authors: S
authors: Bensalma
authors: Corinne
authors: C
authors: Chadéneau
authors: Jean-Marc
authors: JM
authors: Muller
authors: Sébastien
authors: S
authors: Papot
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020719:Glucuronides; D011355:Prodrugs; D014704:Veratrum Alkaloids; C000541:cyclopamine