Bridging the gap between target-based and phenotypic-based drug discovery.

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Drug Discovery Pub Date : 2024-07-01 Epub Date: 2024-05-15 DOI:10.1080/17460441.2024.2355330
Cecília R C Calado
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引用次数: 0

Abstract

Introduction: The unparalleled progress in science of the last decades has brought a better understanding of the molecular mechanisms of diseases. This promoted drug discovery processes based on a target approach. However, despite the high promises associated, a critical decrease in the number of first-in-class drugs has been observed.

Areas covered: This review analyses the challenges, advances, and opportunities associated with the main strategies of the drug discovery process, i.e. based on a rational target approach and on an empirical phenotypic approach. This review also evaluates how the gap between these two crossroads can be bridged toward a more efficient drug discovery process.

Expert opinion: The critical lack of knowledge of the complex biological networks is leading to targets not relevant for the clinical context or to drugs that present undesired adverse effects. The phenotypic systems designed by considering available molecular mechanisms can mitigate these knowledge gaps. Associated with the expansion of the chemical space and other technologies, these designs can lead to more efficient drug discoveries. Technological and scientific knowledge should also be applied to identify, as early as possible, both drug targets and mechanisms of action, leading to a more efficient drug discovery pipeline.

缩小基于靶标和基于表型的药物发现之间的差距。
导言:过去几十年来,科学取得了空前的进步,人们对疾病的分子机制有了更好的了解。这促进了基于靶点方法的药物发现过程。然而,尽管前景广阔,一流药物的数量却在急剧下降:本综述分析了与药物发现过程的主要策略(即基于合理靶点方法和经验表型方法)相关的挑战、进展和机遇。本综述还评估了如何缩小这两个十字路口之间的差距,以实现更高效的药物发现过程:专家观点:由于对复杂的生物网络严重缺乏了解,导致开发出的靶点与临床情况不符,或者开发出的药物产生了不良反应。考虑到现有的分子机制而设计的表型系统可以缩小这些知识差距。随着化学空间和其他技术的扩展,这些设计可以提高药物发现的效率。此外,还应将技术和科学知识用于尽早确定药物靶点和作用机制,从而提高药物发现的效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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