Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Tiantan Xili, Beijing 100050, China.
Expert Opin Drug Discov. 2010 Dec;5(12):1175-88. doi: 10.1517/17460441.2010.529896.
Atherosclerosis is a progressive disease that is characterized by the accumulation of lipid-rich plaques within the artery walls. Despite the past 3 decades witnessing the most significant advances in the pharmacotherapy of atherosclerosis with statins, atherosclerosis is still one of the leading causes of mortality in industrialized and developing nations. The applications of high-throughput screening (HTS) have retrieved hits and lead compounds which may be further developed to new promising therapeutics to achieve more effective reductions in the risk of cardiovascular morbidity and mortality.
The review provides a summary of potential drug targets other than HMG-CoA reductase (primary target of statins) and their application in biochemical or cell-based HTS assays used by pharmaceutical companies and academic laboratories for anti-atherosclerotic drug discovery.
The reader will gain an overview of the HTS strategies currently used in the development of anti-atherosclerotic agents. The reader is also provided with some abortive examples in anti-atherosclerotic drug discovery as well as the associated limitations and challenges of the process that HTS delivers new drugs to treat atherosclerosis.
HTS can assist in the efficient discovery of new drugs towards the potential targets involved in the progress of atherosclerosis.
动脉粥样硬化是一种进行性疾病，其特征是动脉壁内富含脂质的斑块积聚。尽管在过去的 30 年中，他汀类药物在动脉粥样硬化的药物治疗方面取得了最重大的进展，但动脉粥样硬化仍然是工业化和发展中国家死亡的主要原因之一。高通量筛选 (HTS) 的应用已经检索到可能进一步开发为新的有前途的治疗方法的命中和先导化合物，以更有效地降低心血管发病率和死亡率的风险。
综述提供了除 HMG-CoA 还原酶（他汀类药物的主要靶点）以外的潜在药物靶点及其应用的概述，以及制药公司和学术实验室在用于抗动脉粥样硬化药物发现的生化或基于细胞的 HTS 测定中的应用。
读者将全面了解目前用于开发抗动脉粥样硬化药物的 HTS 策略。还向读者提供了抗动脉粥样硬化药物发现中的一些失败实例，以及 HTS 提供治疗动脉粥样硬化的新药的过程中的相关局限性和挑战。
HTS 可以帮助有效地发现针对动脉粥样硬化进展中涉及的潜在靶点的新药。
