Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog
- 作者：Yuqiang Wang ; Jie Jiang ; Xiaojian Jiang ; Shaohui Cai ; Hai Han ; Lianfa Li ; Zhiming Tian ; Wei Jiang ; Zaijun Zhang ; Ying Xiao ; Susan C. Wright ; James W. Larrick
- 关键词：Prodrug ; CC-1065 ; Albumin ; Anticancer
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：1 July 2008
- 卷：16
- 期：13
- 页码：6552-6559
- 文件大小：523 K
摘要
An albumin-binding prodrug of the extremely potent CC-1065 analog, (+)-FDI-CBI, has been synthesized. This analog, (+)-FDI-CBIM, formed an albumin conjugate when added to human albumin in vitro. A greater amount (>3-fold) of the prodrug can be administered to animals compared to the free drug. The prodrug had significantly improved antitumor efficacy compared to the free drug in animal models using syngeneic animal tumors and human ovarian xenografted tumor cells. Antitumor drug delivery by in situ formation of drug–albumin conjugate is a promising strategy to improve antitumor efficacy.