Absorption, distribution, metabolism, and excretion of [14C]SHEN211, a nonpeptidic small-molecule 3CLpro inhibitor, in rats
文献类型：期刊论文
| 作者 | Zhang, Zihao3,4; Jia, Mengting2; Wang, Feiyu3,4; Yang, Chen3; Shi, Huanhuan3; Yuan, Yali3; Tian, Zhuoran2; Ming, Congmei1; Huang, Jinwen1; Pan, Junfang1 |
| 刊名 | JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
 |
| 出版日期 | 2025-07-01 |
| 卷号 | 392期号:7页码:12 |
| 关键词 | SHEN211 3CL p ro inhibitor Mass balance PBPK |
| ISSN号 | 0022-3565 |
| DOI | 10.1016/j.jpet.2025.103623 |
| 通讯作者 | Zheng, Yuandong(zhengyd837@163.com) ; Diao, Xingxing(xxdiao@simm.ac.cn) |
| 英文摘要 | SHEN211 is a selective 3-chymotrypsin-like protease inhibitor that can protect against severe acute respiratory syndrome coronavirus 2. It is currently being assessed in clinical trials in China, but few studies have reported its metabolism in preclinical and clinical settings. This study used radioactive isotope labeling to investigate the absorption, distribution, metabolism, and excretion of SHEN211 in rats. After a single intragastric administration of 2.0 mg/kg (100 mCi/kg) of [14C]SHEN211 in rats, the inhibitor was rapidly absorbed, with feces being the primary route of excretion. The results of tissue distribution indicated that SHEN211-related components were mainly concentrated in the liver. In total, 11 metabolites were identified in rat plasma, urine, feces, and bile, and SHEN211 was the major drug-related component in the systemic circulation. The main metabolic pathways of SHEN211 were N-dealkylation, oxidative defluorination, glucuronidation, and glutathione conjugation. In addition, a physiologically based pharmacokinetic model for rats was constructed and validated using GastroPlus software, and the model was extrapolated to healthy adult males to predict the pharmacokinetic characteristics of SHEN211 in humans, providing invaluable insights into the human mass balance of SHEN211 and paving the way for clinical studies. Significance Statement: This study characterized the absorption, distribution, metabolism, and excretion of SHEN211, a 3CLpro inhibitor for severe acute respiratory syndrome coronavirus 2 in rats. SHEN211 exhibited rapid absorption and was mainly distributed in the liver. Fecal excretion was the primary elimination route. The prediction of human pharmacokinetic characteristics using the physiologically based pharmacokinetic model provides an invaluable reference for optimizing the clinical dosing strategy of SHEN211 and advancing its ongoing clinical trials in China. (c) 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. |
| WOS关键词 | SARS-COV-2 ; TRANSMISSION |
| 资助项目 | JKT Biopharma Co, Ltd ; National Natural Science Foundation of China[82373938] ; National Natural Science Foundation of China[82204585] ; Key Technologies R&D Program of Guangdong Province[2023B1111030004] ; National Key R&D Program of China[2022YFF120260 0] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001530683800001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318843]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zheng, Yuandong; Diao, Xingxing |
| 作者单位 | 1.Convalife Shanghai Co Ltd, Shanghai, Peoples R China 2.Tianjin Univ Tradit Chinese Med, Acad Tradit Chinese Med, Tianjin, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Zihao,Jia, Mengting,Wang, Feiyu,et al. Absorption, distribution, metabolism, and excretion of [14C]SHEN211, a nonpeptidic small-molecule 3CLpro inhibitor, in rats[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2025,392(7):12. |
| APA | Zhang, Zihao.,Jia, Mengting.,Wang, Feiyu.,Yang, Chen.,Shi, Huanhuan.,...&Diao, Xingxing.(2025).Absorption, distribution, metabolism, and excretion of [14C]SHEN211, a nonpeptidic small-molecule 3CLpro inhibitor, in rats.JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,392(7),12. |
| MLA | Zhang, Zihao,et al."Absorption, distribution, metabolism, and excretion of [14C]SHEN211, a nonpeptidic small-molecule 3CLpro inhibitor, in rats".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 392.7(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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