Study of a cyclopamine glucuronide prodrug for the selective chemotherapy of glioblastoma.
The first glucuronide prodrug of the hedgehog signaling inhibitor cyclopamine was synthesized. The carbamoyl derivatisation of cyclopamine significantly decreased its toxicity towards the U87 human glioblastoma cell line. However, when the prodrug was incubated with beta-glucuronidase in the culture media, the active drug was efficiently released thereby restoring its anti-proliferative activity.
Hamon
Florian
F
Université de Poitiers, UMR-CNRS 6514, 40 avenue du Recteur Pineau, 86022 Poitiers, France.
Renoux
Brigitte
B
Chadéneau
Corinne
C
Muller
Jean-Marc
JM
Papot
Sébastien
S
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D020719:Glucuronides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000627:therapeutic use*; D021241:Spectrometry, Mass, Electrospray Ionization; D014704:Veratrum Alkaloids / Q000737:chemistry / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D020719:Glucuronides; D011355:Prodrugs; D014704:Veratrum Alkaloids; C000541:cyclopamine