Design,synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative |
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| Affiliation: | 1. Baruch S. Blumberg Institute, Doylestown, PA, USA;2. Departments of Otorhinolaryngology-Head and Neck Surgery, and Microbiology, and the Tumor Virology Program, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA;1. Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec – Research Center, Québec, QC, Canada;2. Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada;1. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China;2. Department of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou, Jiangxi 341000, PR China;3. Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China;1. Faculty of Arts and Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan;2. Faculty of Pharmacy and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;3. Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;4. Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan;1. Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada;2. Canadian Blood Services, Centre for Innovation (Formerly R&D), Edmonton, Alberta, Canada;3. Terry Fox Laboratory, British Columbia Cancer Agency, Canada;4. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada;5. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada;6. Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada;7. Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada |
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| 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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| Keywords: | Synthesis PEG-A6-conjugated irinotecan Tumor xenograft models Tumor regression |
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