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Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy

文献类型：期刊论文

作者Zhuang, Zhen2,3; Miao, Yu-Ling1; Song, Shan-Shan1; Leng, Guang-Tong2,3; Zhang, Xiao-Fei3; He, Qian3; Ding, Jian1,2; He, Jin-Xue1,2; Yang, Chun-Hao2,3
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-11-05
卷号277页码:17
关键词USP7 inhibitor Structure-activity relationships Anti-cancer pyrrolo[2,3-d]pyrimidin-4-one
ISSN号0223-5234
DOI10.1016/j.ejmech.2024.116752
通讯作者He, Jin-Xue(jinxue_he@simm.ac.cn) ; Yang, Chun-Hao(chyang@simm.ac.cn)
英文摘要USP7 is one of the most studied deubiquitinating enzymes, which is involved in the regulation of multiple cell signaling pathways and has been shown to be associated with the occurrence and progression of a variety of cancers. Inhibitors targeting USP7 have been studied by several teams, but most of them lack selectivity and have low activities. Herein, we reported a serious of pyrrole[2,3-d]pyrimidin-4-one derivatives through scaffold hopping of recently reported 4-hydroxypiperidine compounds. The representative compound Z33 (YCH3124) exhibited highly potent USP7 inhibition activity as well as anti-proliferative activity against four kinds of cancer cell lines. Further study revealed that YCH3124 effectively inhibited the downstream USP7 pathway and resulted in the accumulation of both p53 and p21 in a dose-dependent manner. Notably, YCH3124 disrupted cell cycle progression through restricting G1 phase and induced significant apoptosis in CHP-212 cells. In summary, our efforts provided a series of novel pyrrole[2,3-d]pyrimidin-4-one analogs as potent USP7 inhibitors with excellent anti-cancer activity.
WOS关键词STRUCTURE-GUIDED DEVELOPMENT ; CELLS
资助项目National Natural Sci-ence Foundation of China[82073875] ; State Key Laboratory of Drug Research[SIMM2103ZZ-03]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001294851100001
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/312830]  
专题新药研究国家重点实验室
通讯作者He, Jin-Xue; Yang, Chun-Hao
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Canc Res Ctr, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhuang, Zhen,Miao, Yu-Ling,Song, Shan-Shan,et al. Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2024,277:17.
APA Zhuang, Zhen.,Miao, Yu-Ling.,Song, Shan-Shan.,Leng, Guang-Tong.,Zhang, Xiao-Fei.,...&Yang, Chun-Hao.(2024).Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,277,17.
MLA Zhuang, Zhen,et al."Discovery of pyrrolo[2,3-d]pyrimidin-4-one derivative YCH3124 as a potent USP7 inhibitor for cancer therapy".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 277(2024):17.

入库方式： OAI收割

来源：上海药物研究所

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