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 β-glucuronidase in the culture media, the active drug was efficiently released thereby restoring its anti-proliferative activity.

Graphical abstractThe glucuronide prodrug 1 of the hedgehog signaling inhibitor cyclopamine was synthesized and evaluated as a potential selective antitumor agent for the treatment of glioblastoma.Figure optionsDownload full-size imageDownload as PowerPoint slide