个人中心| | 帮助
高级检索
当前位置： 首页 > 详情页

Design, synthesis and biological evaluation of naphthyl amide derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors

| 认领 | 导出 | |

文献详情

资源类型：
Pubmed体系：
作者：
Yu Quanwei[1,2] * ; Song Chao[1,2] ; Bi Liyun[1,3] ; Zhao Shuang[1,4,5] ; Lei Qian[1,2,4,5] ; Yang Na[1,2] ; Chen Hai[1,2,3,4,5] ; Wang Yuxi[1,2,3,4,5,*1] ; He Yang[1,2,3,4,5,*1] ; Deng Hui[1,2,3,4,5,*1] ;
机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Institute of Respiratory Health, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3]Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4]The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China [5]State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Chengdu, Sichuan, China
出处：
DOI： 10.1016/j.bmc.2024.117844
ISSN：

关键词： Monoacylglycerol lipase Inhibitor discovery Reversible inhibitors Activity-based protein profiling Anti-cancer agents

摘要：
Monoacylglycerol lipase (MAGL) is a key enzyme responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG), and has attracted great interest due to its involvement in various physiological and pathological processes, such as cancer progression. In the past, a number of covalent irreversible inhibitors have been reported for MAGL, however, experimental evidence highlighted some drawbacks associated with the use of these irreversible agents. Therefore, efforts were mainly focused on the development of reversible MAGL inhibitor in recent years. Here, we designed and synthesized a series of naphthyl amide derivatives (12-39) as another type of reversible MAGL inhibitors, exemplified by ± 34, which displayed good MAGL inhibition with a pIC50 of 7.1, and the potency and selectivity against endogenous MAGL were further demonstrated by competitive ABPP. Moreover, the compound showed appreciable antiproliferative activities against several cancer cells, including H460, HT29, CT-26, Huh7 and HCCLM-3. The investigations culminated in the discovery of the naphthyl amide derivative ± 34, and it may represent as a new scaffold for MAGL inhibitor development, particularly for the reversible ones.Copyright © 2024 Elsevier Ltd. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China (No. 22277084, 21807076, 82104264, 82373721), the Sichuan Natural Science Foundation (No. 2024NSFSC0754, 2023NSFSC1671, 2022NSFSC0055, 2019YJ0112).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 3 区 医学
小类 | 2 区 有机化学 3 区 生化与分子生物学 3 区 药物化学
最新[2025]版：
大类 | 3 区 医学
小类 | 2 区 有机化学 3 区 生化与分子生物学 3 区 药物化学
第一作者：
第一作者机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Institute of Respiratory Health, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
通讯作者：
通讯机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Institute of Respiratory Health, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3]Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4]The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China [5]State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Chengdu, Sichuan, China [*1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China
推荐引用方式(GB/T 7714)：
Yu Quanwei,Song Chao,Bi Liyun,et al.Design, synthesis and biological evaluation of naphthyl amide derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors[J].Bioorganic & Medicinal Chemistry.2024,111:117844.doi:10.1016/j.bmc.2024.117844.
APA：
Yu Quanwei,Song Chao,Bi Liyun,Zhao Shuang,Lei Qian...&Deng Hui.(2024).Design, synthesis and biological evaluation of naphthyl amide derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors.Bioorganic & Medicinal Chemistry,111,
MLA：
Yu Quanwei,et al."Design, synthesis and biological evaluation of naphthyl amide derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors".Bioorganic & Medicinal Chemistry 111.(2024):117844

相关文献

[1]Optimization of a naphthyl amide class identifies potent and selective reversible monoacylglycerol lipase (MAGL) inhibitors [2]Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer [3]Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review [4]Exploration of novel isoxazole-fused quinone derivatives as anti-colorectal cancer agents through inhibiting STAT3 and elevating ROS level [5]Current advances and development strategies of targeting son of sevenless 1 (SOS1) in drug discovery [6]Discovery of Coumarin as Microtubule Affinity-Regulating Kinase 4 Inhibitor That Sensitize Hepatocellular Carcinoma to Paclitaxel. [7]The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor. [8]Discovery of a Potent GLUT Inhibitor from a Library of Rapafucins by Using 3D Microarrays. [9]Design, synthesis and biological evaluation of indazole derivatives as selective covalent inhibitors of FGFR4 in wild-type and gatekeeper mutants [10]Discovery of a novel small-molecule inhibitor of Fam20C that induces apoptosis and inhibits migration in triple negative breast cancer.

资源点击量：65780 今日访问量：0 总访问量：5151 更新日期：2025-12-01 建议使用谷歌、火狐浏览器 常见问题

版权所有©2020 四川省肿瘤医院 技术支持：重庆聚合科技有限公司 地址：成都市人民南路四段55号