中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Structure-Based Drug Design of 2-Amino-[1,1′-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer

文献类型：期刊论文

作者Wang, Chaofan7; Fang, Yan4,5,6; Zhou, Ziqin7; Liu, Zhuoheng7; Feng, Fang5,6; Wan, Xuan4,5,6; Li, Yan5,6; Liu, Shuang3; Ding, Jian4,5,6; Zhang, Zhi-Min7
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-08-20
页码21
ISSN号0022-2623
DOI10.1021/acs.jmedchem.4c01458
通讯作者Zhang, Zhi-Min(zhangzm@jnu.edu.cn) ; Xie, Hua(hxie@simm.ac.cn) ; Lu, Xiaoyun(luxy2016@jnu.edu.cn)
英文摘要CCNE1 amplification occurs in breast cancer and currently lacks effective therapies. PKMYT1 as a synthetic lethal target for CCNE1 amplification holds promise for the treatment of CCNE1-amplified breast cancer. Herein, we discover a series of 2-amino-[1,1 '-biphenyl]-3-carboxamide derivatives as potent and selective PKMYT1 inhibitors using structure-based drug design. The representative compound 8ma exhibited excellent potency against PKMYT1, while sparing WEE1. It also suppressed proliferation of the CCNE1-amplified HCC1569 breast cancer cell line and showed synergistic cytotoxicity in combination with gemcitabine. PKMYT1 X-ray cocrystallography confirmed that introduction of key binding interactions between the inhibitors and residues Asp251 and Tyr121 of PKMYT1 greatly enhanced the potency and selectivity of the compounds.
WOS关键词AMPLIFICATION
资助项目Changjiang Scholars Award Program of Ministry of Education ; National Natural Science Foundation of China[8247131133] ; National Natural Science Foundation of China[82273763] ; Guangdong Basic and Applied Basic Research Foundation[2024B1515040007] ; Guangdong Basic and Applied Basic Research Foundation[2022B1515130008] ; Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation[2020B1212060034] ; High-Performance Public Computing Service Platform of Jinan University
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001295109800001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/312821]  
专题新药研究国家重点实验室
通讯作者Zhang, Zhi-Min; Xie, Hua; Lu, Xiaoyun
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
3.Jinan Univ, Guangdong Prov Gen Hosp 2, Dept Hematol, Guangzhou 510632, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Div Antitumor Pharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
7.Jinan Univ, Sch Pharm, State Key Lab Bioact Mol & Druggabil Assessment, Int Cooperat Lab Tradit Chinese Med Modernizat & I, Guangzhou 510632, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Chaofan,Fang, Yan,Zhou, Ziqin,et al. Structure-Based Drug Design of 2-Amino-[1,1′-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024:21.
APA Wang, Chaofan.,Fang, Yan.,Zhou, Ziqin.,Liu, Zhuoheng.,Feng, Fang.,...&Lu, Xiaoyun.(2024).Structure-Based Drug Design of 2-Amino-[1,1′-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer.JOURNAL OF MEDICINAL CHEMISTRY,21.
MLA Wang, Chaofan,et al."Structure-Based Drug Design of 2-Amino-[1,1′-biphenyl]-3-carboxamide Derivatives as Selective PKMYT1 Inhibitors for the Treatment of CCNE1-Amplified Breast Cancer".JOURNAL OF MEDICINAL CHEMISTRY (2024):21.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。