Urea-containing peptide boronic acids as potent proteasome inhibitors

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• 作者：Li-Qiang Han^a ; Xia Yuan^a ; Xing-Yu Wu^a ; Ri-Dong Li^a ; Bo Xu^a ; Qing Cheng^a ; Zhen-Ming Liu^a ; Tian-Yan Zhou^a ; Hao-Yun An^b ; Xin Wang^a ; Tie-Ming Cheng^a ; Ze-Mei Ge^a ; ^{zmge@bjmu.edu.cn} ; Jing-Rong Cui^a ; ^{jrcui@bjmu.edu.cn} ; Run-Tao Li^a ; ^{lirt@bjmu.edu.cn}
• 关键词：Urea-containing peptide boronic acids ; Proteasome inhibitor ; Anti-tumor activity ; Structure-activity relationship ; Low toxicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：925-939
• 全文大小：2399 K
• 卷排序：125

文摘

Two series of novel urea-containing peptide boronic acids were designed and synthesized as proteasome inhibitors. The SAR was investigated and one of the two series showed impressive anti-proteasome and anti-tumor activities. More human tumor cell lines were tested and compound I-14 was selected to evaluate its anticancer activity in vivo. Compound I-14 showed obvious in vivo anticancer activity with much lower toxicity comparing to Bortezomib.