化学
炎症
受体
髓样
体内
Toll样受体
髓系细胞
药理学
癌症研究
脂多糖
细胞生物学
免疫学
先天免疫系统
生物化学
生物
遗传学
作者
Lingfeng Chen,Hongjin Chen,Pengqin Chen,Wenxin Zhang,Chao Wu,Chao Sun,Wei Luo,Lulu Zheng,Zhiguo Liu,Guang Liang
标识
DOI:10.1016/j.ejmech.2018.09.068
摘要
Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll-like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases.
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