Mooberry Susan L
Southwest Foundation for Biomedical Research.
Methods Mol Med. 2007;137:289-302. doi: 10.1007/978-1-59745-442-1_20.
Taxol, the first microtubule stabilizer identified, is one of the most important new anticancer drugs to be brought to the clinic in the past 20 yr. The clinical success of TaxolTM led to the development of a second-generation taxane, docetaxel (Taxotere), and multiple third-generation taxane derivatives are under development. Non-taxane microtubule-stabilizers of diverse chemical structures, including the epothilones and discodermolide, show promising preclinical activities and several epothilones are progressing through clinical trials. One important advantage of the new stabilizers is their ability to circumvent drug resistance mechanisms. The clinical development of these new classes of agents suggests that microtubule stabilizers will continue to be important drugs for the treatment of cancer. This chapter provides a brief history of Taxol and the discovery and development status of other classes of microtubule stabilizers. Although all microtubule-stabilizers share similar mechanisms of action, interesting subtle differences among the stabilizers are being detected. This chapter also provides some strategies for identifying the differences among microtubule stabilizers that may help prioritize them for development and clinical use.
紫杉醇是首个被鉴定出的微管稳定剂，是过去20年里进入临床的最重要的新型抗癌药物之一。紫杉醇的临床成功促使了第二代紫杉烷类药物多西他赛（泰索帝）的研发，并且多种第三代紫杉烷衍生物也正在研发中。包括埃坡霉素和盘尼西龙在内的具有不同化学结构的非紫杉烷类微管稳定剂显示出有前景的临床前活性，并且几种埃坡霉素正在进行临床试验。这些新型稳定剂的一个重要优势是它们规避耐药机制的能力。这些新型药物的临床研发表明微管稳定剂将继续成为治疗癌症的重要药物。本章简要介绍了紫杉醇的历史以及其他类微管稳定剂的发现和研发状况。尽管所有微管稳定剂都具有相似的作用机制，但正在检测到稳定剂之间有趣的细微差异。本章还提供了一些识别微管稳定剂之间差异的策略，这可能有助于确定它们开发和临床应用的优先级。
