药物开发中基于细胞的方法——简评

Q4 Biochemistry, Genetics and Molecular Biology Medical Journal of Cell Biology Pub Date : 2020-03-01 DOI:10.2478/acb-2020-0005
I. Kocherova, B. Kempisty, Greg Hutchings, Lisa Moncrieff, C. Dompe, Krzysztof Janowicz, J. Petitte, J. Shibli, P. Mozdziak
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引用次数: 2

摘要

摘要体外模型代表了药物开发过程中体内或离体研究的一种替代技术。基于细胞的测定用于测量培养细胞的增殖和毒性水平,以及信号通路的激活和形态变化。体外进行的研究旨在评估新合成的药物渗透生物屏障并发挥其治疗或细胞毒性作用的能力。然而,由于缺乏确认的疗效,超过一半的研究药物在第二或第三阶段的临床试验中失败。大约三分之一的药物因安全问题而失效,例如不可接受的毒性水平。为了降低药物开发中的损耗水平,考虑实施转化表型分析以及破译新分子实体的各种分子作用机制至关重要。在这篇综述中,我们总结了药物研究中最常用的现有基于细胞的方法,并考虑了它们的优缺点。运行标题:基于细胞的药物开发方法
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Cell-based approaches in drug development – a concise review
Abstract In vitro models represent an alternative technique to in vivo or ex vivo studies in the drug development process. Cell-based assays are used to measure the level of proliferation and toxicity, as well as activation of signalling pathways and changes in morphology in cultivated cells. The studies conducted in vitro are aimed to estimate the newly synthesised drugs’ ability to permeate biological barriers and exert their therapeutic or cytotoxic effects. However, more than half of all studied drugs fail in the second or third phase of clinical trials due to a lack of confirmed efficacy. About a third of drugs fail because of safety issues, such as unacceptable levels of toxicity. To reduce attrition level in drug development, it is crucial to consider the implementation of translational phenotypic assays as well as to decipher various molecular mechanisms of action for new molecular entities. In this review, we summarise the existing cell-based methods most frequently used in the studies on drugs, taking into account their advantages and drawbacks. Running title: Cell-based approaches in drug development
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来源期刊
Medical Journal of Cell Biology
Medical Journal of Cell Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
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