The High-Resolution Solution Structure of Epothilone A Bound to Tubulin: An Understanding of the Structure–Activity Relationships for a Powerful Class of Antitumor Agents

✍ Scribed by Teresa Carlomagno; Marcel J. J. Blommers; Jens Meiler; Wolfgang Jahnke; Thomas Schupp; Frank Petersen; Dieter Schinzer; Karl-Heinz Altmann; Christian Griesinger

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 122 KB
• Volume: 42
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200351276

✦ Synopsis

Most of the drugs available today for the treatment of cancer are based on the inhibition of cell proliferation and induction of cell death by apoptosis. At the molecular level, the majority of cytotoxic agents interfere with DNA function. However, a prominent subclass of compounds, including paclitaxel (taxol), exert their cytotoxic activity by perturbing microtubule dynamics. In 1993, Höfle, Reichenbach, and coworkers reported the isolation and characterization of a novel class of cytotoxic polyketide macrolides from the myxobacterium Sorangium cellulosum, which were named epothilones (1). [1,2] The interest in these natural products immediately soared when it was found that epothilones are microtubule stabilizers and that they inhibit cell proliferation through a mechanism of action analogous to that of the renowned clinical anticancer drug taxol. [3] Epothilones exhibit extraordinary antiproliferative activity in vitro and they efficiently induce cell death in paclitaxel-resistant tumor cell lines at up to 5000-fold

[*] Dr.