Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors
文献类型：期刊论文
| 作者 | Fan, Tiantian1,2; Ji, Yinchun3; Chen, Danqi1 ; Peng, Xia3; Ai, Jing2,3,4; Xiong, Bing1,2
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| 刊名 | JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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| 出版日期 | 2023 |
| 卷号 | 38期号:1页码:282-293 |
| 关键词 | RIPK2 inhibitor NOD immunity inflammation |
| ISSN号 | 1475-6366 |
| DOI | 10.1080/14756366.2022.2148317 |
| 通讯作者 | Ai, Jing(jai@simm.ac.cn) ; Xiong, Bing(bxiong@simm.ac.cn) |
| 英文摘要 | Receptor-interacting protein kinase 2 (RIPK2) is an essential protein kinase mediating signal transduction by NOD1 and NOD2, which play an important role in regulating immune signalling. In this study, we designed and synthesised a novel series of 4-aminoquinoline-based derivatives as RIPK2 inhibitors. In vitro, compound 14 exhibited high affinity (IC50 = 5.1 +/- 1.6 nM) and excellent selectivity to RIPK2 showing in a dendrogram view of the human kinome phylogenetic tree. Bearing favourable lipophilicity and eligible lipophilic ligand efficiency (LipE), compound 14 was selected to investigate cellular anti-inflammatory effect and was identified as a potent inhibitor to reduce the secretion of MDP-induced TNF-alpha with a dose-dependent manner. Moreover, compound 14 showed moderate stability in human liver microsome. Given these promising results, compound 14 could serve as a favourable inhibitor of RIPK2 for further physiological and biochemical research so as to be used in therapeutic treatment. |
| WOS关键词 | POTENT ; IDENTIFICATION ; PEPTIDOGLYCAN |
| 资助项目 | Natural Science Foundation of China for Innovation Research Group ; Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning ; [81821005] ; [2020CXJQ02] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000889114500001 |
| 出版者 | TAYLOR & FRANCIS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304551]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ai, Jing; Xiong, Bing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China 4.Hangzhou Inst Adv Study UCAS, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Tiantian,Ji, Yinchun,Chen, Danqi,et al. Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors[J]. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,2023,38(1):282-293. |
| APA | Fan, Tiantian,Ji, Yinchun,Chen, Danqi,Peng, Xia,Ai, Jing,&Xiong, Bing.(2023).Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors.JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,38(1),282-293. |
| MLA | Fan, Tiantian,et al."Design, synthesis and biological evaluation of 4-aminoquinoline derivatives as receptor-interacting protein kinase 2 (RIPK2) inhibitors".JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 38.1(2023):282-293. |
入库方式： OAI收割
来源：上海药物研究所
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