Discovery of novel TLR2 antagonists as anti-inflammatory agents
文献类型：期刊论文
| 作者 | Tang, Xuehang4; Qi, Luyao2,3; Li, Yingxia4; Tang, Wei1,2,3; Zhang, Wei4 |
| 刊名 | BIOORGANIC CHEMISTRY
 |
| 出版日期 | 2025-09-01 |
| 卷号 | 164页码:15 |
| 关键词 | Toll-like receptor 2 TLR2 antagonists Structure-activity relationship Anti-inflammatory |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2025.108805 |
| 通讯作者 | Li, Yingxia(liyx417@fudan.edu.cn) ; Tang, Wei(tangwei@simm.ac.cn) ; Zhang, Wei(zhangw416@fudan.edu.cn) |
| 英文摘要 | Toll-like receptors (TLRs) were the first identified pattern recognition receptors of the innate immune system. In TLRs family, Toll-like receptor 2 (TLR2) is notable for its extensive expression across various tissues and its ability to recognize a diverse array of pathogenic microorganisms and their products. However, long term or excessive activation of TLR2 can lead to inflammatory, autoimmune disorders and neurodegenerative diseases. Modulation of TLR2 function by small molecules is considered as a promising strategy for the treatment of these diseases. Among the reported TLR2 antagonists, MMG-11, as a selective TLR2 antagonist with low cytotoxicity, can effectively inhibit excessive TLR2 activation and the production of inflammatory factors. However, MMG-11 contained the pyrogallol fragment which reduces the metabolic stability and synthetic accessibility. Meanwhile, the biological activity of MMG-11 needs to be further improved. Herein we designed and synthesized a series of TLR2 antagonists starting from MMG-11 for improving antagonistic activity and metabolic stability. Among thirty tested compounds, T30 exhibited better inhibitory activity and metabolic stability than MMG-11 (T30 IC50 = 11.41 +/- 0.83 mu M vs MMG-11 IC50 = 22.58 +/- 0.97 mu M; T30 T1/2 = 16.67 min vs MMG-11 T1/2 = 7.88 min). T30 also showed reasonable toxicity profiles and deserved further research. |
| WOS关键词 | TOLL-LIKE RECEPTOR-2 ; IMMUNE-SYSTEM |
| 资助项目 | Qingdao Na-tional Laboratory for Marine Science and Technology[2022ONLM030003-2] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001547096200002 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321225]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Yingxia; Tang, Wei; Zhang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Antiinflammat & Immunopharmacol, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tang, Xuehang,Qi, Luyao,Li, Yingxia,et al. Discovery of novel TLR2 antagonists as anti-inflammatory agents[J]. BIOORGANIC CHEMISTRY,2025,164:15. |
| APA | Tang, Xuehang,Qi, Luyao,Li, Yingxia,Tang, Wei,&Zhang, Wei.(2025).Discovery of novel TLR2 antagonists as anti-inflammatory agents.BIOORGANIC CHEMISTRY,164,15. |
| MLA | Tang, Xuehang,et al."Discovery of novel TLR2 antagonists as anti-inflammatory agents".BIOORGANIC CHEMISTRY 164(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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