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Cancer Chemotherapy: A Paclitaxel Prodrug for ADEPT (Antibody‐Directed Enzyme Prodrug Therapy)
Author(s) -
Schmidt Frédéric,
Ungureanu Ioana,
Duval Romain,
Pompon Alain,
Monneret Claude
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200106)2001:11<2129::aid-ejoc2129>3.0.co;2-#
Subject(s) - adept , prodrug , chemistry , paclitaxel , chemotherapy , pharmacology , enzyme , cancer , cancer chemotherapy , cancer therapy , biochemistry , medicine
A glucuronide‐based prodrug of paclitaxel (taxol ® ) has been synthesized for use in antibody‐directed enzyme prodrug therapy (ADEPT). This three‐component prodrug was obtained by coupling a glucuronyl derivative of N ‐methylamino 4‐nitrophenol ( 10 ) to the 2′‐hydroxy group of the side‐chain of paclitaxel through an aromatic carbamate. Once deprotected, prodrug 2 was shown to be relatively stable in human serum, and to be significantly less cytotoxic (IC 50 = 65 μ M and 90 n M , respectively) than the parent drug. As expected, compound 2 efficiently releases taxol in the presence of β‐glucuronidase.