Validating Small Molecule Chemical Probes for Biological Discovery.

IF 12.1 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Annual review of biochemistry Pub Date : 2022-04-01 DOI:10.1146/annurev-biochem-032620-105344

Victoria Vu, Magdalena M. Szewczyk, David Y. Nie, C. Arrowsmith, D. Barsyte-Lovejoy

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引用次数: 8

Abstract

Small molecule chemical probes are valuable tools for interrogating protein biological functions and relevance as a therapeutic target. Rigorous validation of chemical probe parameters such as cellular potency and selectivity is critical to unequivocally linking biological and phenotypic data resulting from treatment with a chemical probe to the function of a specific target protein. A variety of modern technologies are available to evaluate cellular potency and selectivity, target engagement, and functional response biomarkers of chemical probe compounds. Here, we review these technologies and the rationales behind using them for the characterization and validation of chemical probes. In addition, large-scale phenotypic characterization of chemical probes through chemical genetic screening is increasingly leading to a wealth of information on the cellular pharmacology and disease involvement of potential therapeutic targets. Extensive compound validation approaches and integration of phenotypic information will lay foundations for further use of chemical probes in biological discovery. Expected final online publication date for the Annual Review of Biochemistry, Volume 91 is June 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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用于生物发现的小分子化学探针的验证。

小分子化学探针是询问蛋白质生物学功能和作为治疗靶点的相关性的有价值的工具。严格验证化学探针参数，如细胞效力和选择性，对于明确将化学探针处理产生的生物学和表型数据与特定靶蛋白的功能联系起来至关重要。多种现代技术可用于评估化学探针化合物的细胞效力和选择性、靶标参与和功能反应生物标志物。在这里，我们回顾了这些技术及其用于化学探针表征和验证的原理。此外，通过化学遗传筛选对化学探针进行大规模表型表征，越来越多地为潜在治疗靶点的细胞药理学和疾病参与提供了丰富的信息。广泛的化合物验证方法和表型信息的整合将为化学探针在生物学发现中的进一步应用奠定基础。《生物化学年度评论》第91卷预计最终在线出版日期为2022年6月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。

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

Annual review of biochemistry 生物-生化与分子生物学

CiteScore

33.90

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0.00%

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期刊介绍： The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.

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