Pendri A, Conover C D, Greenwald R B
Enzon Inc., Piscataway, NJ 08854-3969, USA.
Anticancer Drug Des. 1998 Jul;13(5):387-95.
Synthesis and in vivo antitumor activity evaluation of water-soluble poly(ethylene glycol) (PEG)-conjugated paclitaxel-2'-glycinate (6) are reported. This prodrug demonstrated enhanced antitumor activity and less toxicity in a P388/0 murine leukemia model when compared, on an equimolar basis, with native paclitaxel formulated in Cremophor/ethanol. Employing 6 in the treatment of HT-29, A549 and SKOV3 solid tumor-bearing xenografted mice demonstrated significant antitumor activity. The outstanding performance of 6 may be attributed partly to the tripartate nature of the prodrug.
报道了水溶性聚乙二醇（PEG）共轭紫杉醇-2'-甘氨酸酯（6）的合成及体内抗肿瘤活性评价。在P388/0小鼠白血病模型中，与用聚氧乙烯蓖麻油/乙醇配制的天然紫杉醇等摩尔相比，该前药表现出增强的抗肿瘤活性和更低的毒性。在治疗携带HT-29、A549和SKOV3实体瘤的异种移植小鼠中使用6显示出显著的抗肿瘤活性。6的优异性能可能部分归因于前药的三方性质。
