Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation
文献类型：期刊论文
| 作者 | Chen, Lili1,3 ; Zhang, Zhuang2; Tian, Hongtao3; Jiang, Shan2; Ji, Yunyun2; Liu, Mengru2; Shen, Jianhua3; Cao, Zhengyu2; Wang, Kai3
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2022-08-15 |
| 卷号 | 68页码:11 |
| ISSN号 | 0968-0896 |
| 关键词 | TRPC5 AC1903 Podocyte FSGS Keratinocyte Proliferation Inflammation |
| DOI | 10.1016/j.bmc.2022.116853 |
| 通讯作者 | Cao, Zhengyu(zycao@cpu.edu.cn) ; Wang, Kai(kwang@simm.ac.cn) |
| 英文摘要 | Transient receptor potential canonical (TRPC) channels are a class of non-selective cation channels expressed in a variety of tissues and organ systems where they functionally regulate physiological and pathological processes. TRPC5 has been shown to be a promising target for focal segmental glomerulosclerosis treatment. In this study, we report the synthesis and biological evaluation of a novel series of benzimidazole-based TRPC5 inhibitors. One compound, 8b, is 100-fold more potent than the parent compound, AC1903, in the suppression of TRPC5 channel activity. Interestingly, both AC1903 and 8b also suppressed TRPC4 channel activity with similar potency. Compound 8b also significantly blunts protamine sulfate-induced reorganization of podocyte cytoskeleton, interleukin (IL)-17-induced cell proliferation, and the expression of proinflammatory mediators in human keratinocyte HaCaT cells. |
| WOS关键词 | TRPC5 |
| 资助项目 | National Natural Science Foundation of China[82073683] ; National Natural Science Foundation of China[21777192] ; National Natural Science Foundation of China[81903826] ; Youth Innovation Promotion Association, Chinese Academy of Sciences[2019282] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000861772700005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302652]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cao, Zhengyu; Wang, Kai |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCM Pharmacol, Jiangsu Key Lab TCM Evaluat & Translat Res, 639 Long Mian Rd, Nanjing 211198, Jiangsu, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med SIMM, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Lili,Zhang, Zhuang,Tian, Hongtao,et al. Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2022,68:11. |
| APA | Chen, Lili.,Zhang, Zhuang.,Tian, Hongtao.,Jiang, Shan.,Ji, Yunyun.,...&Wang, Kai.(2022).Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation.BIOORGANIC & MEDICINAL CHEMISTRY,68,11. |
| MLA | Chen, Lili,et al."Synthesis of AC1903 analogs as potent transient receptor potential canonical channel 4/5 inhibitors and biological evaluation".BIOORGANIC & MEDICINAL CHEMISTRY 68(2022):11. |
入库方式： OAI收割
来源：上海药物研究所
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