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用于鉴定风湿性自身免疫性炎症疾病新疗法的药物重新定位策略

Drug Repositioning Strategies for the Identification of Novel Therapies for Rheumatic Autoimmune Inflammatory Diseases.

作者信息

Grammer Amrie C, Lipsky Peter E

机构信息

AMPEL BioSolutions and RILITE Research Institute, 250 West Main Street, Suite 300, Charlottesville, VA 22902, USA.

AMPEL BioSolutions and RILITE Research Institute, 250 West Main Street, Suite 300, Charlottesville, VA 22902, USA.

出版信息

Rheum Dis Clin North Am. 2017 Aug;43(3):467-480. doi: 10.1016/j.rdc.2017.04.010.

Abstract

Rheumatic Autoimmune Inflammatory Diseases such as Sjögren's and lupus lack modern treatments. Less than 5% of drugs approved by the FDA from 2014 to mid-2016 had a RAID indication. Many RAID standard-of-care drugs were repurposed based on serendipitous observations, similarity-of-disease categorization, and/or off-target effects. Recently, drug repurposing has become more intentional, relying on an evolving awareness of molecular underpinnings, as well as a better understanding of drug-target interactions by computational modeling. Understanding mechanisms of disease pathogenesis can be synergistic in identifying new drug candidates and target pathways using unbiased Big-Data repositioning approaches as genomics, PheWAS (disease mechanism-of-action), GWAS and/or epigenetic-profiling.

摘要

干燥综合征和狼疮等风湿性自身免疫性炎症疾病缺乏现代治疗方法。2014年至2016年年中,美国食品药品监督管理局(FDA)批准的药物中,只有不到5%有风湿性自身免疫性炎症疾病(RAID)适应症。许多RAID标准治疗药物是基于偶然观察、疾病分类相似性和/或脱靶效应而重新利用的。最近,药物重新利用变得更加有针对性,这依赖于对分子基础认识的不断发展,以及通过计算模型对药物-靶点相互作用的更好理解。利用基因组学、全基因组关联研究(PheWAS,疾病作用机制)、全基因组关联分析(GWAS)和/或表观遗传分析等无偏大数据重新定位方法,了解疾病发病机制在识别新的候选药物和靶点途径方面可能具有协同作用。

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