Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog.
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.
Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China. yqwangphd@yahoo.com
Yuqiang
Y
Wang
Jie
J
Jiang
Xiaojian
X
Jiang
Shaohui
S
Cai
Hai
H
Han
Lianfa
L
Li
Zhiming
Z
Tian
Wei
W
Jiang
Zaijun
Z
Zhang
Ying
Y
Xiao
Susan C
SC
Wright
James W
JW
Larrick
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000080890:Duocarmycins; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000080890:Duocarmycins; D007211:Indoles; D011355:Prodrugs; D012709:Serum Albumin; C018782:CC 1065