Design and Development of a Novel Oral 4′-Fluorouridine Double Prodrug VV261 against SFTSV
文献类型：期刊论文
| 作者 | Cheng, Yong4,5,7; Zheng, Wei2; Dong, Xinru5,6; Sun, Tengxiao4,5,7; Xu, Mengwei6; Xiang, Li4,5,7; Li, Jian4,5,7; Wang, Huilong4,5; Jian, Xiaoqin5,6; Yu, Jingjin2 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-04-28 |
| 卷号 | 68期号:9页码:9811-9826 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.5c00626 |
| 英文摘要 | 4 '-Fluorouridine (4 '-FU), despite demonstrating potent anti-SFTSV efficacy in vitro and in vivo, faces hindrances in its further development as a promising drug due to its weak chemical stability. Here, we report the discovery and development of VV261, a novel 4 '-FU double prodrug with three isobutyryl groups on the ribose moiety and a nicotinoyloxymethyl group linked to the imide-nitrogen on the base moiety, exhibiting notable chemical stability and favorable pharmacokinetic properties. In SFTSV-infected mice, VV261 at 5 mg/kg/d for 7 days demonstrated complete protection against lethal SFTSV infection, prevented weight loss, and even a 2 day treatment significantly reduced both viral RNA copies and infectious virus titers in multiple organs, and notably alleviated splenic tissue lesions. After further preclinical evaluations, VV261, identified as a promising candidate drug for the treatment of SFTS, has entered Phase I clinical trials in China, the first such candidate to reach this stage for SFTS. |
| WOS关键词 | VIRUS |
| 资助项目 | Chinese Academy of Sciences[2021YFC0865000] ; Chinese Academy of Sciences[2022YFC2303300] ; National Key Research and Development Program of China[SIMM0120231003] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[XDB0490000] ; Strategic Priority Research Program of Chinese Academy of Sciences[2022CFA099] ; Hubei Natural Science Foundation for Distinguished Young Scholars |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001478130500001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317548]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Aisa, Haji A.; Xie, Yuanchao; Xiao, Gengfu; Shen, Jingshan |
| 作者单位 | 1.Hubei Jiangxia Lab, Wuhan 430200, Peoples R China 2.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China 3.Xinjiang Med Univ, Sch Pharm, Urumqi 830054, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol & Biosafety, Wuhan 430071, Peoples R China 7.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plants, Urumqi 830011, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Yong,Zheng, Wei,Dong, Xinru,et al. Design and Development of a Novel Oral 4′-Fluorouridine Double Prodrug VV261 against SFTSV[J]. JOURNAL OF MEDICINAL CHEMISTRY,2025,68(9):9811-9826. |
| APA | Cheng, Yong.,Zheng, Wei.,Dong, Xinru.,Sun, Tengxiao.,Xu, Mengwei.,...&Shen, Jingshan.(2025).Design and Development of a Novel Oral 4′-Fluorouridine Double Prodrug VV261 against SFTSV.JOURNAL OF MEDICINAL CHEMISTRY,68(9),9811-9826. |
| MLA | Cheng, Yong,et al."Design and Development of a Novel Oral 4′-Fluorouridine Double Prodrug VV261 against SFTSV".JOURNAL OF MEDICINAL CHEMISTRY 68.9(2025):9811-9826. |
入库方式： OAI收割
来源：上海药物研究所
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