Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors
文献类型：期刊论文
| 作者 | Zhang, Zhuang1; Chen, Lili2,3 ; Tian, Hongtao3; Liu, Mengru1; Jiang, Shan1; Shen, Jianhua3; Wang, Kai3; Cao, Zhengyu1
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2022-04-01 |
| 卷号 | 61页码:11 |
| 关键词 | TRPC5 Pyrroledione FSGS CKD |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2022.128612 |
| 通讯作者 | Wang, Kai(kwang@simm.ac.cn) ; Cao, Zhengyu(zycao@cpu.edu.cn) |
| 英文摘要 | A deepening understanding of the relationship between transient receptor potential canonical channel 5 (TRPC5) and chronic kidney disease (CKD), has led to the emergence of several types of TRPC5 inhibitors displaying clear therapeutic effect. Herein, we report the synthesis and biological evaluation of a series of pyrroledione TRPC5 inhibitors, culminating in the discovery of compound 16g with subtype selectivity. Compared with GFB-8438, a potent TRPC5 inhibitor (Goldfinch Bio), compound 16g showed improved inhibition of TRPC5 and enhanced protective effect against protamine sulfates (PS)-induced podocyte injury in vitro. In addition, compound 16g did not induce cell death in primary cultured hepatocytes and immortalized podocytes in a preliminary toxicity assessment, indicating its utility as a potent and safe inhibitor for studying the function of TRPC5. |
| WOS关键词 | KIDNEY-DISEASE ; CALCIUM |
| 资助项目 | Science and Technology Commission of Shanghai Municipality (STCSM)[19431900900] ; 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 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000783582200006 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299788]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Kai; Cao, Zhengyu |
| 作者单位 | 1.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Jiangsu Key Lab TCM Evaluat & Translat Res, 639 Long Mian Rd, Nanjing 211198, Jiangsu, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, 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 | Zhang, Zhuang,Chen, Lili,Tian, Hongtao,et al. Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2022,61:11. |
| APA | Zhang, Zhuang.,Chen, Lili.,Tian, Hongtao.,Liu, Mengru.,Jiang, Shan.,...&Cao, Zhengyu.(2022).Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,61,11. |
| MLA | Zhang, Zhuang,et al."Discovery of pyrroledione analogs as potent transient receptor potential canonical channel 5 inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 61(2022):11. |
入库方式： OAI收割
来源：上海药物研究所
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