Benzothiazole amide analogues as antagonists of TRPC 6 channels: A therapeutic approach for kidney fibrosis
文献类型：期刊论文
| 作者 | Ren, Chunlin1,2,5; Xu, Qiding1,2,5; Luo, Qiusi1,2,5; Qiao, Xue1,2,5; Ding, Taotao1,2,5; Wang, Wumei2,3; Zeng, Xiaodong1,5; Chen, Cheng4; Xiao, Yuling1,2,5; Hong, Xuechuan1,2,3,5 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-07-05 |
| 卷号 | 291页码:16 |
| 关键词 | Transient receptor potential canonical 6 channels Antagonist Renal fibrosis Benzothiazole derivatives Unilateral ureteral obstruction |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2025.117628 |
| 英文摘要 | Transient receptor potential canonical 6 (TRPC6) channels, which function as receptor-operated, non-selective cation channels, are widely expressed in the kidney, lungs, and brain. Within these organs, they play crucial roles in regulating diverse physiological processes and contribute to the pathogenesis of various disorders. The resolution of the cryo-electron microscopy structure of TRPC6 has significantly advanced our understanding of its molecular mechanisms, thereby providing a robust platform for structure-based drug design. Building upon compound 1S as a lead, we developed and synthesized a series of benzothiazole derivatives, ultimately identifying compound X26 as a potent TRPC6 antagonist with an IC50 of 0.97 mu M. In vitro administration of X26 significantly suppressed TGF-beta 1-induced myofibroblast differentiation in HK-2 cells, as evidenced by a reduced expression of alpha-SMA, collagen I, and fibronectin. Furthermore, in a unilateral ureteral obstruction (UUO)- induced kidney fibrosis mouse model, treatment with X26 resulted in a substantial reduction in serum urea nitrogen, serum creatinine, and urinary protein levels, as well as a decrease in renal collagen deposition. These findings establish X26 as a promising lead for the development of TRPC6 antagonists and therapeutic interventions for kidney fibrosis. |
| WOS关键词 | RENAL FIBROSIS ; INHIBITION ; MECHANISMS ; DISCOVERY ; TARGET ; ENTRY |
| 资助项目 | Guangdong Basic and Applied Basic Research Foundation[JCYJ20230807090100002] ; Taishan Scholar Project of Shandong Province[2023A1515012649] ; Shandong Provincial Natural Science Foundation[TSQN202306320] ; Tibet Autonomous Region Science and Technology Plan Project Key Project[ZR2024QH253] ; Natural Science Foundation of Shandong Province[XZ202301ZY0014G] ; Natural Science Foundation of Shandong Province[LSKJ202445] ; Shandong Laboratory Program[ZR2023MB085] ; Interdisciplinary Innovative Foundation of Zhongnan Hospital[SYS202205] ; [ZNJC202413] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001477777400001 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317530]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zeng, Xiaodong; Chen, Cheng; Xiao, Yuling; Hong, Xuechuan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Wuhan Univ, Zhongnan Hosp, Sch Pharmaceut Sci, Dept Cardiol, Wuhan 430071, Peoples R China 3.Wuhan Univ, Shenzhen Inst, Shenzhen 518057, Peoples R China 4.Wuhan Univ, Div Nephrol, Renmin Hosp, Wuhan 430060, Peoples R China 5.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Chunlin,Xu, Qiding,Luo, Qiusi,et al. Benzothiazole amide analogues as antagonists of TRPC 6 channels: A therapeutic approach for kidney fibrosis[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2025,291:16. |
| APA | Ren, Chunlin.,Xu, Qiding.,Luo, Qiusi.,Qiao, Xue.,Ding, Taotao.,...&Hong, Xuechuan.(2025).Benzothiazole amide analogues as antagonists of TRPC 6 channels: A therapeutic approach for kidney fibrosis.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,291,16. |
| MLA | Ren, Chunlin,et al."Benzothiazole amide analogues as antagonists of TRPC 6 channels: A therapeutic approach for kidney fibrosis".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 291(2025):16. |
入库方式： OAI收割
来源：上海药物研究所
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