Saito Ryuta, Yano Naoko, Kojima Shinji, Miyoshi Fumihiko
Discovery Technology Laboratories, Sohyaku Innovative Research Division, Mitsubishi Tanabe Pharma Corporation.
Nihon Yakurigaku Zasshi. 2023;158(1):10-14. doi: 10.1254/fpj.22072.
To improve the decreased efficiency of drug discovery and development, drug repurposing (also called drug repositioning) has been expected, that it is a strategy for identifying new medical indications for approved, investigational or suspended drugs. Particularly, according to the rapid expansion of medical and life science data and the remarkable technological progress of AI technology in recent years, the approach of computational drug repurposing has been attracted as one of the applications in data-driven drug discovery. Computational drug repurposing is a method of systematical and strategical research for identifying novel indication candidates and prioritizing the indication candidates based on the various profiles of drugs, genes, and diseases. In this review article, the typical data science techniques for data-driven drug repurposing, 1. drug-target interaction prediction, 2. transcriptomics-based approach by using differentially gene expression profiles, 3. natural language processing and word embedding, and their current status were summarized. We have also introduced a use case of data-driven drug repurposing for the PPARγ/α agonist Netoglitazone that we actually analyzed. In addition, as an excellent successful case of data-driven drug repurposing in recent years, we have also discussed a repurposing case reported by BenevolentAI in 2020, that Baricitinib has been identified as a potential intervention for COVID-19, based on immunomodulatory treatment by its mechanism of action as a JAK1 and JAK2 inhibition.
为了提高药物研发效率的下降问题,药物重新利用(也称为药物重新定位)备受期待,它是一种为已批准、正在研究或暂停使用的药物确定新医学适应症的策略。特别是,近年来随着医学和生命科学数据的迅速扩展以及人工智能技术的显著技术进步,计算药物重新利用方法作为数据驱动药物发现的应用之一受到了关注。计算药物重新利用是一种基于药物、基因和疾病的各种特征,系统地、战略性地研究以识别新的适应症候选物并对其进行优先级排序的方法。在这篇综述文章中,总结了用于数据驱动药物重新利用的典型数据科学技术:1. 药物-靶点相互作用预测;2. 使用差异基因表达谱的基于转录组学的方法;3. 自然语言处理和词嵌入,以及它们的现状。我们还介绍了我们实际分析的PPARγ/α激动剂奈格列净的数据驱动药物重新利用的一个用例。此外,作为近年来数据驱动药物重新利用的一个出色成功案例,我们还讨论了BenevolentAI在2020年报道的一个重新利用案例,即基于巴瑞替尼作为JAK1和JAK2抑制剂的作用机制进行免疫调节治疗,已确定其为COVID-19的潜在干预药物。