埃博霉素新药研发与技术创新初探

Review of the R&D and technology innovation of epothilones as new drugs

埃博霉素类化合物是一种新型抗肿瘤药物,通过与肿瘤细胞中的微管蛋白结合,促进微管蛋白聚合并抑制微管的解聚,使细胞周期停止,最终诱导细胞凋亡。已经或正在开发的几种埃博霉素类似物有伊沙匹隆、埃博霉素B、沙戈匹隆、埃博霉素D、21-氨基埃博霉素B和KOS-1584,特别是沙戈匹隆极有可能成为高效候选抗肿瘤新药。本文对具有代表性的几个埃博霉素类化合物的临床药代动力学及其毒性反应研究进行综述并从结构特点和作用机制出发,重点论述伊沙匹隆和沙戈匹隆的研发和技术创新。

Epothilone analogues are a new type of antitumor drugs, which can promote the polymerization of tublin heterodimers into microtubule polymers, stabilize microtubules against depolymerzation, and induce mitotic cell cycle arrest and eventually apoptosis. The epothilones which have been or are being developed are ixabepilone, epothilone B, ZK-EPO （ sagopilone）, KOS-862 （ epothilone D）, BMS-310705 （21-amino-epothilone B） and KOS-1584, among which ZK-EPO has high potential to become an effective candidate of antitumor agent. In this article, the clinical pharmacokinetics and adverse reactions of several epothilone analogues are reviewed, and the research progress of ixabepilone and ZK-EPO is summarized with focus on their structures and mechanisms.