Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog.
Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog.
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CC-1065类似物白蛋白结合前药的合成和抗肿瘤活性评价。
DOI：
10.1016/j.bmc.2008.05.025
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发表时间：
2008
影响因子：
3.5
通讯作者：
Larrick,JamesW
中科院分区：
文献类型：
--
作者：
Wang,Yuqiang;Jiang,Jie;Jiang,Xiaojian;Cai,Shaohui;Han,Hai;Li,Lianfa;Tian,Zhiming;Jiang,Wei;Zhang,Zaijun;Xiao,Ying;Wright,SusanC;Larrick,JamesW
合成了极强的CC-1065类似物的白蛋白结合前药(+)-fDi-CBI。该类似物(+)-FDI-CBIM在体外与人血清白蛋白形成白蛋白偶联物。与免费药物相比，动物可以服用更多的前药(>；3倍)。在使用同基因动物肿瘤和人卵巢异种移植瘤细胞的动物模型中，与游离药物相比，前药显著提高了抗肿瘤效果。药物-白蛋白原位结合物给药是提高抗肿瘤疗效的一种很有前途的策略。
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.