Discovery of potential novel TRPC5 inhibitors by virtual screening and bioassay
文献类型：期刊论文
| 作者 | Shen,Meiling; Li,Lingfeng; Li,Yue; Gu,Xi; Bai,Longhui; Xia,Chengfeng; Xiong,Wenyong ; Zuo,Zhili
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2023 |
| 卷号 | 94页码:117477 |
| 关键词 | TRPC5 Inhibitors Virtual screening Ca 2+channel CHANNELS IDENTIFICATION PERMEABILITY CALCIUM |
| ISSN号 | 1464-3391 |
| DOI | 10.1016/j.bmc.2023.117477 |
| 英文摘要 | The transient receptor potential canonical channel 5 (TRPC5), a member of the TRPC family, plays a crucial role in the regulation of various physiological activities and diseases, including those related to the central nervous system, cardiovascular system, kidney, and cancer. As a nonselective cation channel, TRPC5 mainly controls the influx of extracellular Ca2+ into cells, thereby modulating cellular depolarization and intracellular ion concen-tration. Inhibition of TRPC5 by small molecules presents a promising approach for the treatment of TRPC5-associated diseases. In this study, we conducted a comprehensive virtual screening of more than 1.5 million molecules from the Chemdiv database (https://www.chemdiv.com) to identify potential inhibitors of hTRPC5, utilizing the published structures and binding sites of hTRPC5 as a basis. Lipinski's rule, Veber's rule, PAINS filters, pharmacophore analysis, molecular docking, ADMET evaluation and cluster analysis methods were applied for the screening. From this rigorous screening process, 18 candidates exhibiting higher affinities to hTRPC5 were subsequently evaluated for their inhibitory effects on Ca2+ influx using a fluorescence-based assay. Notably, two molecules, namely SML-1 and SML-13, demonstrated significant inhibition of intracellular Ca2+ levels in hTRPC5-overexpressing HEK 293T cells, with IC50 values of 10.2 mu M and 10.3 mu M, respectively. These findings highlight SML-1 and SML-13 as potential lead molecules for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases. |
| WOS记录号 | WOS:001079364500001 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/75458]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Shen,Meiling,Li,Lingfeng,Li,Yue,et al. Discovery of potential novel TRPC5 inhibitors by virtual screening and bioassay[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2023,94:117477. |
| APA | Shen,Meiling.,Li,Lingfeng.,Li,Yue.,Gu,Xi.,Bai,Longhui.,...&Zuo,Zhili.(2023).Discovery of potential novel TRPC5 inhibitors by virtual screening and bioassay.BIOORGANIC & MEDICINAL CHEMISTRY,94,117477. |
| MLA | Shen,Meiling,et al."Discovery of potential novel TRPC5 inhibitors by virtual screening and bioassay".BIOORGANIC & MEDICINAL CHEMISTRY 94(2023):117477. |
入库方式： OAI收割
来源：昆明植物研究所
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