Biovista Inc., Charlottesville, VA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2011 May-Jun;3(3):323-34. doi: 10.1002/wsbm.147. Epub 2011 Feb 16.
Drug repurposing is the process of using existing drugs in indications other than the ones they were originally designed for. It is an area of significant recent activity due to the mounting costs of traditional drug development and scarcity of new chemical entities brought to the market by bio-pharmaceutical companies. By selecting drugs that already satisfy basic toxicity, ADME and related criteria, drug repurposing promises to deliver significant value at reduced cost and in dramatically shorter time frames than is normally the case for the drug development process. The same process that results in drug repurposing can also be used for the prediction of adverse events of known or novel drugs. The analytics method is based on the description of the mechanism of action of a drug, which is then compared to the molecular mechanisms underlying all known adverse events. This review will focus on those approaches to drug repurposing and adverse event prediction that are based on the biomedical literature. Such approaches typically begin with an analysis of the literature and aim to reveal indirect relationships among seemingly unconnected biomedical entities such as genes, signaling pathways, physiological processes, and diseases. Networks of associations of these entities allow the uncovering of the molecular mechanisms underlying a disease, better understanding of the biological effects of a drug and the evaluation of its benefit/risk profile. In silico results can be tested in relevant cellular and animal models and, eventually, in clinical trials.
药物重定位是指将现有药物用于最初设计用途以外的适应症的过程。由于传统药物开发成本不断增加,以及生物制药公司推向市场的新化学实体稀缺,该领域最近非常活跃。通过选择已经满足基本毒性、ADME 和相关标准的药物,药物重定位有望以更低的成本和比通常情况下更短的时间框架提供显著的价值。导致药物重定位的相同过程也可用于预测已知或新型药物的不良事件。该分析方法基于对药物作用机制的描述,然后将其与所有已知不良事件的分子机制进行比较。这篇综述将重点介绍基于生物医学文献的药物重定位和不良事件预测方法。此类方法通常从文献分析开始,旨在揭示基因、信号通路、生理过程和疾病等看似不相关的生物医学实体之间的间接关系。这些实体的关联网络可以揭示疾病的分子机制,更好地了解药物的生物学效应,并评估其获益/风险状况。计算机模拟结果可以在相关的细胞和动物模型中进行测试,最终可以在临床试验中进行测试。