Synthesis and evaluation of hybrid molecules as RIPK1 and HDACs dual inhibitors
文献类型：期刊论文
| 作者 | Tang, Mingze5,6; Zhou, Xuan3,4,5; Shen, Qianqian4; Fang, Chen2,3,6; Peng, Xia4,5; Ji, Yinchun4; Zhu, Guijun5,6; Geng, Meiyu3,4,5 ; Chen, Yi1,4,5; Duan, Wenhu1,5,6
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| 刊名 | JOURNAL OF MOLECULAR STRUCTURE
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| 出版日期 | 2024-12-15 |
| 卷号 | 1318页码:13 |
| 关键词 | Receptor -interacting protein kinase 1 Histone deacetylases Inhibitor Molecular dynamics (MD) simulation ADMET analysis |
| ISSN号 | 0022-2860 |
| DOI | 10.1016/j.molstruc.2024.139238 |
| 通讯作者 | Ai, Jing(jai@simm.ac.cn) ; Zhang, Hefeng(zhanghefeng1@simm.ac.cn) |
| 英文摘要 | Receptor-interacting protein kinase 1 (RIPK1) is a key target in the necroptosis signaling pathway, and histone deacetylases (HDACs) are crucial epigenetic modifiers for various proteins. Both RIPK1 and HDACs are critical for homeostasis and inflammation, and their dysfunction were observed concurrently in many diseases, including cancer, neurodegenerative disorders, acute injuries, inflammatory diseases, and autoimmune diseases. Thus, simultaneous inhibition of RIPK1 and HDACs may offer promising strategies for the treatment of these diseases. In this research, we adopted a hybrid design strategy and synthesized a series of RIPK1/HDACs dual inhibitors. Among them, compound 4 demonstrated potent inhibitory activities against both RIPK1 and HDACs with nanomolar level potency. Molecular docking and molecular dynamics (MD) simulations confirmed that compound 4 could bind to RIPK1 and HDAC6 with high affinity. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis suggested that compound 4 possesses promising drug-likeness profiles. Overall, this study provided potent RIPK1/HDACs dual inhibitor for future study of RIPK1 and HDACs in disease. |
| WOS关键词 | HISTONE DEACETYLASE ; NECROPTOSIS ; TARGETS |
| 资助项目 | Natural Science Foundation of China for Innovation Research Group[81821005] ; Project of Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0120231001] ; Shandong Laboratory Program[SYS202205] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001270709800001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312386]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Ai, Jing; Zhang, Hefeng |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Canc Res Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, Small Mol Drug Res Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, Mingze,Zhou, Xuan,Shen, Qianqian,et al. Synthesis and evaluation of hybrid molecules as RIPK1 and HDACs dual inhibitors[J]. JOURNAL OF MOLECULAR STRUCTURE,2024,1318:13. |
| APA | Tang, Mingze.,Zhou, Xuan.,Shen, Qianqian.,Fang, Chen.,Peng, Xia.,...&Zhang, Hefeng.(2024).Synthesis and evaluation of hybrid molecules as RIPK1 and HDACs dual inhibitors.JOURNAL OF MOLECULAR STRUCTURE,1318,13. |
| MLA | Tang, Mingze,et al."Synthesis and evaluation of hybrid molecules as RIPK1 and HDACs dual inhibitors".JOURNAL OF MOLECULAR STRUCTURE 1318(2024):13. |
入库方式： OAI收割
来源：上海药物研究所
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