The Resurrection of Phenotypic Drug Discovery,ACS Medicinal Chemistry Letters

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The Resurrection of Phenotypic Drug Discovery
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2020-03-06 , DOI: 10.1021/acsmedchemlett.0c00006
Wayne E Childers ₁ , Khaled M Elokely _{1,

2,

3} , Magid Abou-Gharbia ₁

Affiliation

Prior to genetic mapping, the majority of drug discovery efforts involved phenotypic screening, wherein compounds were screened in either in vitro or in vivo models thought to mimic the disease state of interest. While never completely abandoning phenotypic approaches, the labor intensive nature of such tests encouraged the pharmaceutical industry to move away from them in favor of target-based drug discovery, which facilitated throughput and allowed for the efficient screening of large numbers of compounds. However, a consequence of reliance on target-based screening was an increased number of failures in clinical trials due to poor correlation between novel mechanistic targets and the actual disease state. As a result, the field has seen a recent resurrection in phenotypic drug discovery approaches. In this work, we highlight some recent phenotypic projects from our industrial past and in our current academic drug discovery environment that have provided encouraging results.

中文翻译：

表型药物发现的复兴

在基因作图之前，大多数药物发现工作涉及表型筛选，其中化合物在体外或体内模型中筛选，被认为模拟感兴趣的疾病状态。虽然从未完全放弃表型方法，但此类测试的劳动密集型性质鼓励制药行业摆脱它们，转而支持基于目标的药物发现，这促进了通量并允许对大量化合物进行有效筛选。然而，由于新的机制目标与实际疾病状态之间的相关性较差，依赖基于目标的筛选的结果是临床试验中失败的次数增加。因此，该领域最近在表型药物发现方法中复苏。在这项工作中，

更新日期：2020-03-06

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