Lynch James J, Van Vleet Terry R, Mittelstadt Scott W, Blomme Eric A G
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
J Pharmacol Toxicol Methods. 2017 Sep;87:108-126. doi: 10.1016/j.vascn.2017.02.020. Epub 2017 Feb 16.
Most pharmaceutical companies test their discovery-stage proprietary molecules in a battery of in vitro pharmacology assays to try to determine off-target interactions. During all phases of drug discovery and development, various questions arise regarding potential side effects associated with such off-target pharmacological activity. Here we present a scientific literature curation effort undertaken to determine and summarize the most likely functional and pathological outcomes associated with interactions at 70 receptors, enzymes, ion channels and transporters with established links to adverse effects. To that end, the scientific literature was reviewed using an on-line database, and the most commonly reported effects were summarized in tabular format. The resultant table should serve as a practical guide for research scientists and clinical investigators for the prediction and interpretation of adverse side effects associated with molecules interacting with components of this screening battery.
大多数制药公司会在一系列体外药理学试验中测试其处于发现阶段的专有分子,以试图确定脱靶相互作用。在药物发现和开发的各个阶段,都会出现有关此类脱靶药理活性相关潜在副作用的各种问题。在此,我们开展了一项科学文献整理工作,以确定并总结与70种已证实与不良反应有关联的受体、酶、离子通道和转运蛋白相互作用时最可能出现的功能和病理结果。为此,我们使用在线数据库对科学文献进行了综述,并以表格形式总结了最常报道的效应。所得表格应为研究科学家和临床研究人员预测和解释与该筛选组合成分相互作用的分子相关不良副作用提供实用指南。