Recent Developments in the Maytansinoid Antitumor Agents

• Published in: Chemical & Pharmaceutical Bulletin Vol. 52; no. 1; pp. 1 - 26
• Main Authors: Cassady, John M., Chan, Kenneth K., Floss, Heinz G., Leistner, Eckhard
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2004; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Actinosynnema pretiosum; Animals; ansamitocin; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - therapeutic use; Antineoplastic Agents, Phytogenic - toxicity; antitumor activity; Bacteria - metabolism; biosynthesis; Biotransformation; Bryophyta - chemistry; Clinical Trials as Topic; Humans; maytansine; Maytansine - analogs & derivatives; Maytansine - chemistry; Maytansine - therapeutic use; Maytansine - toxicity; Plants, Medicinal - chemistry; Plants, Medicinal - genetics; Protein Engineering; Structure-Activity Relationship; tumor-specific antibody
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.52.1

Maytansine and its congeners have been isolated from higher plants, mosses and from an Actinomycete, Actinosynnema pretiosum. Many of these compounds are antitumor agents of extraordinary potency, yet phase II clinical trials with maytansine proved disappointing. The chemistry and biology of maytansinoids has been reviewed repeatedly in the late 1970s and early 1980s; the present review covers new developments in this field during the last two decades. These include the use of maytansinoids as "warheads" in tumor-specific antibodies, preliminary metabolism studies, investigations of their biosynthesis at the biochemical and genetic level, and ecological issues related to the occurrence of such typical microbial metabolites in higher plants.