使用体外二级药理学小组对临床停药化合物进行综合分析,以预测药物开发过程中的潜在安全风险

IF 3.7 Q1 CHEMISTRY, MEDICINAL
Verena Albert, Danielle E. Skinner, Saloni Karnwal, Lauren N. Guili, Miguel Vazquez, Omar Ledezma, Rebecca Shaffer, Aura Celniker, Alexander De La Cruz, Matthew Caliendo, Andrew M. Hanna, Luciano Galdieri, Alastair J. King, Nicole B. Servant and Mirza Jahic*, 
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引用次数: 0

摘要

体外二级药理学仍然是药物发现的关键工具,用于在候选药物进入临床开发之前评估潜在的脱靶相互作用。其主要目的是减少药物不良反应引起的临床损耗,提高患者安全。一种被广泛采用的方法包括对广泛靶点的安全药理学分析,通常侧重于具有确定治疗靶点的化学系列。利用强大的高通量筛选平台,如Eurofins Discovery的SAFETYscan47,可以快速识别和减轻发现化合物中的潜在风险。本文通过比较临床失败的候选药物与更广泛的化合物模态数据集,强调了体外药理学分析的效用。通过更彻底地评估SAFETYscan47产生的数据,我们的目标是展示体外分析如何在临床前发现过程中提供有价值的见解,最终支持患者安全并减少临床损耗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive Analysis of Clinically Discontinued Compounds Using an In Vitro Secondary Pharmacology Panel to Predict Potential Safety Risks during Drug Development

In vitro secondary pharmacology remains a critical tool in pharmaceutical drug discovery for evaluating potential off-target interactions before lead candidates advance into clinical development. Its primary aim is to reduce clinical attrition caused by adverse drug reactions and enhance patient safety. A widely adopted approach involves safety pharmacological profiling across a broad panel of targets, typically focusing on a chemical series with an identified therapeutic target. Utilizing a robust high-throughput screening platform, such as SAFETYscan47 from Eurofins Discovery, enables the rapid identification and mitigation of potential liabilities within discovery compounds. This article highlights the utility of in vitro pharmacological profiling by comparing clinically failed drug candidates against a broader compound modality data set. By more thoroughly evaluating the data generated through SAFETYscan47, we aim to demonstrate how in vitro profiling can offer valuable insights during preclinical discovery, ultimately supporting patient safety and reducing clinical attrition.

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来源期刊
ACS Pharmacology and Translational Science
ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)
CiteScore
10.00
自引率
3.30%
发文量
133
期刊介绍: ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.
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