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Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative
Yang-Qing Huang1, Jian-Dong Yuan2, Hai-Feng Ding2
1Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210096, China; Bright Gene Bio-Medical Technology Co., Ltd., Suzhou 215123, China; School of Pharmacy, Guilin Medical University, Guilin 541004, China.
Abstract:
A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.
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