Dalvi Tanay, Dewangan Bhaskar, Das Rudradip, Rani Jyoti, Shinde Suchita D, Vhora Nazmina, Jain Alok, Sahu Bichismita
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 380054, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 380054, India.
Cent Nerv Syst Agents Med Chem. 2020;20(3):157-176. doi: 10.2174/1871524920666201021164805.
The most common reason behind dementia is Alzheimer's disease (AD) and it is predicted to be the third life-threatening disease apart from stroke and cancer for the geriatric population. Till now, only four drugs are available on the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidence of molecular targets are the major hurdles for developing a new drug to treat AD. The rate of attrition of many advanced drugs at clinical stages makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repurposing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) consists of 27 candidates, and around half of the number are drugs which have already been approved for other indications. Although in the past, the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we have reviewed the clinical candidates for AD with emphasis on their development history, including molecular targets and the relevance of the target for AD.
痴呆症最常见的病因是阿尔茨海默病（AD），预计它将成为老年人群除中风和癌症之外的第三大致命疾病。到目前为止，市场上仅有四种药物可用于缓解症状。疾病病理生理学的复杂性以及缺乏分子靶点的确凿证据是开发治疗AD新药的主要障碍。许多晚期药物在临床阶段的淘汰率使得从头发现新药的过程成本非常高昂。相比之下，药物再利用（DR）是以一种不那么繁琐且经济的方式开发治疗AD药物的一种有吸引力的工具。因此，人们一直在通过筛选和数据挖掘对旧药进行再利用来努力开发治疗AD的新药。例如，对处于III期临床试验阶段（截至2019年2月）的在研药物的调查显示有27种候选药物，其中约一半是已被批准用于其他适应症的药物。尽管过去已经从疾病领域、分子靶点的角度对AD的药物再利用过程进行了综述，但对于近期药物研发管线（2019 - 2020年）中用于AD的再利用药物却没有系统的综述。在本手稿中，我们重点回顾了AD的临床候选药物，包括它们的研发历史，分子靶点以及该靶点与AD的相关性。
