毒理学相关资料,第八章内容参考文献6.pdfVIP

424 Microtubule-stabilizing agents: a growing class of important anticancer drugs Karl-Heinz Altmann Microtubule-stabilizing agents continue to play an important role have been established to share the taxanes’ ability to inhib- in anticancer drug discovery and development. New agents it the depolymerization of microtubules, and these were again discovered in the past year, including small synthetic discoveries have opened new perspectives for the develop- molecules. At least three new taxanes and two compounds of ment of a next generation of Taxol-like clinical anticancer the epothilone class of natural products underwent clinical trials agents. These compounds include epothilones A and B in 2000. Unexpected new findings about synergistic effects [5–7,8• • ], discodermolide [9–12], eleutherobin [13–15,16 ], between different microtubule-stabilizing agents in vitro raise sarcodictyins A and B [16• • ,17,18], laulimalide [19 ], and new prospects for combination chemotherapy. FR182877 (also known as WS9885B) [20–22], whose struc- tures are depicted in Figure 1 together with those of a Addresses number of (non-natural) analogs, which will also be Novartis Pharma AG, Corporate Research, WKL-136.5.22, addressed in this article. The general biological properties of CH-4002 Basel; e-mail: karl-heinz.altmann@ most of these agents have been reviewed [23–27] and shall Current Opinion in Chemical Biology 2001, 5:424–431