Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog

  • Bioorg Med Chem. 2008 Jul 1;16(13):6552-9. doi: 10.1016/j.bmc.2008.05.025.
Yuqiang Wang  1 ,  Jie Jiang ,  Xiaojian Jiang ,  Shaohui Cai ,  Hai Han ,  Lianfa Li ,  Zhiming Tian ,  Wei Jiang ,  Zaijun Zhang ,  Ying Xiao ,  Susan C Wright ,  James W Larrick
Affiliations
  • 1. Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China. [email protected]
PMID: 18508273 DOI: 10.1016/j.bmc.2008.05.025
Abstract

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.