Discovery of Triazole Nucleosides with Potent Anticancer Activity Against Drug-resistant Pancreatic

来源 :中国上海第七届国际新药发明科技年会 | 被引量 : 0次 | 上传用户:sz10088
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  Pancreatic cancer is one of the most lethal forms of human cancer.The current first-line treatment is based on Gemcitabine,a nucleoside drug,which is only moderately effective,yielding merely a 12% response rate and a median survival time of five months.There is therefore an urgent need for more efficacious drugs to treat pancreatic cancer.We aim to develop novel triazole nucleosides as drug candidates for pancreatic cancer and have discovered a dozen of active molecules showing potent and selective anticancer activity against drug-resistant pancreatic cancer MiaPaCa-2 cells,with much better potency than the reference drug Gemcitabine.In addition,results obtained from FACS flow cytometry and caspase-3 activity assay indicated that these compounds have caspase-dependent apoptosis-induced anticancer activity.Further in vivo study was carried out using nude mice bearing MiaPaCa-2-xenografed tumors:60% regression in tumor volume was achieved after only two weeks treatment.
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