Cancer chemotherapy: A paclitaxel prodrug for ADEPT (antibody-directed enzyme prodrug therapy)

A glucuronide-based prodrug of paclitaxel (taxol((R))) has been synthesized for use in antibody-directed enzyme prodrug therapy (ADEPT). This three-co mponent prodrug was obtained by coupling a glucuronyl derivative of N-methy lamino 4-nitrophenol (10) to the 2'-hydroxy group of the side-chain of pacl itaxel through an aromatic carbamate. Once deprotected, prodrug 2 was shown to be relatively stable in human serum, and to be significantly less cytot oxic (IC50 = 65 muM and 90 nM, respectively) than the parent drug. As expec ted, compound 2 efficiently releases taxol in the presence of beta -glucuro nidase.