细胞依赖的ProTide产药的激活及其对抗病毒研究的影响
Yueting Liu1, Shuxin Sun1, Jiapeng Li1
1Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, Michigan 48109, United States.
ACS pharmacology & translational science
|October 19, 2023
概括
抗病毒前药物特诺福维尔阿拉芬胺 (TAF) 和索福斯布维尔 (SOF) 的激活因细胞系而异. Huh-7细胞的激活效率最高,而Vero E6细胞的激活效率最低.
科学领域:
- 药理学 药理学是指药理学的学科.
- 病毒学 病毒学
- 生物化学 生物化学
背景情况:
- 普罗泰德前药物增强细胞透性和核酸抗病毒药物的细胞内激活.
- 之前的体外研究表明,在不同细胞系中,ProTide前药的激活是可变的.
研究的目的:
- 在五种常见的抗病毒研究细胞系中研究诺福维尔阿拉芬胺 (TAF) 和索福斯布维尔 (SOF) 的激活特征.
- 为了将激活效率与关键激活酶和药物载体的表达相关联.
主要方法:
- 在Vero E6,Huh-7,Calu-3,A549和Caco-2细胞系中评估TAF和SOF的激活.
- 分析了使用文献和蛋白质组数据库对碳氧化酶1的蛋白质表达,甲素A,胺三核酸结合蛋白1的蛋白质表达,P-糖蛋白和OATPs.
主要成果:
- TAF和SOF激活显示出显著的细胞依赖性变异性,Huh-7细胞是最有效的,Vero E6细胞是最不有效的.
- 与SOF相比,TAF在所有测试的细胞系中表现出更高的激活率.
- 在细胞系中观察到激活酶和转运体表达模式的差异,这可能解释了观察到的激活变异性.
结论:
- 细胞系选择对于准确评估核酸/核酸原药的抗病毒疗效至关重要.
- 激活酶和载体丰度的变化强调了在抗病毒药物开发中需要谨慎的实验设计.
更多相关视频
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
7.7K
09:29Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
30.3K
相关概念视频
01:29Immune Response Against Viral Pathogens
798
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
798
01:30Prodrugs
2.6K
Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
Prodrugs help overcome...
2.6K