Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays
Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays
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通过基于结构的虚拟筛选和体外生物测定发现了减轻小胶质细胞炎症激活的新型 MIF 抑制剂
DOI：
10.1038/s41401-021-00753-x
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发表时间：
2021-08
影响因子：
8.2
通讯作者：
Zheng Long-Tai
中科院分区：
文献类型：
--
作者：
Zhang Yu;Xu Lei;Zhang Yao;Pan Jie;Wang Pu-qing;Tian Sheng;Li Huan-ting;Gao Bo-wen;Hou Ting-jun;Zhen Xue-chu;Zheng Long-Tai
Macrophage migration inhibitory factor (MIF) is a pluripotent pro-inflammatory cytokine and is related to acute and chronic inflammatory responses, immune disorders, tumors, and other diseases. In this study, an integrated virtual screening strategy and bioassays were used to search for potent MIF inhibitors. Twelve compounds with better bioactivity than the prototypical MIF-inhibitor ISO-1 (IC50= 14.41 μM) were identified by an in vitro enzymatic activity assay. Structural analysis revealed that these inhibitors have novel structural scaffolds. Compound11was then chosen for further characterization in vitro, and it exhibited marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs). Our findings suggest that MIF may be involved in the regulation of microglial inflammatory activation and that small-molecule MIF inhibitors may serve as promising therapeutic agents for neuroinflammatory diseases.
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影响因子：
3.8
作者：
通讯作者：
--
基于多种蛋白质结构的结合分子对接和药效团搜索的综合虚拟筛选策略的开发和评估
影响因子：
5.6
作者：
Li, Youyong;Pan, Peichen;Li, Dan;Hou, Tingjun
通讯作者：
Hou, Tingjun
影响因子：
7.3
作者：
Orita, M;Yamamoto, S;Tanaka, A
通讯作者：
Tanaka, A
影响因子：
2.7
作者：
Cisneros, Jose A.;Robertson, Michael J.;Jorgensen, William L.
通讯作者：
Jorgensen, William L.
巨噬细胞是巨噬细胞迁移抑制因子的重要且以前未被认可的来源。
影响因子：
15.3
作者：
Calandra, Thierry;Bernhagen, Juergen;Mitchell, Robert A.;Bucala, Richard
通讯作者：
Bucala, Richard