使用DiscoveRx PathHunter β -阻滞蛋白测定表征大麻素CB2受体配体。

Q2 Chemistry

Journal of Biomolecular Screening Pub Date : 2009-01-01 DOI:10.1177/1087057108327329

Debra McGuinness, Asra Malikzay, Richard Visconti, Karen Lin, Marvin Bayne, Frederick Monsma, Charles A Lunn

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引用次数: 56

摘要

作者在基于细胞的受体/ β -抑制素相互作用试验(DiscoveRx PathHunter)中表征了一组大麻素CB(2)受体配体，包括三芳基双砜逆激动剂。结果与竞争配体结合试验的结果进行了比较，并与福斯克林刺激的cAMP水平(PerkinElmer LANCE)的影响进行了比较。作者展示了三种检测系统之间良好的相关性，β -抑制蛋白互补检测比cAMP检测大麻素CB(2)激动剂显示出更强的信号。进一步的实验验证表明，DiscoveRx PathHunter HEK293 CB(2) β -抑制蛋白实验可以从冷冻保存的细胞悬液中进行，消除了在活细胞筛选活动中需要多个细胞池引起的变化。这些结果，以及作者评估一组随机文库化合物的结果，验证了使用配体诱导的人类大麻素CB(2)受体和β -阻滞素之间的相互作用作为大麻素CB(2)受体特异性化合物的适当和有价值的筛选平台。

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Characterizing cannabinoid CB2 receptor ligands using DiscoveRx PathHunter beta-arrestin assay.

The authors have characterized a set of cannabinoid CB(2) receptor ligands, including triaryl bis sulfone inverse agonists, in a cell-based receptor/beta-arrestin interaction assay (DiscoveRx PathHunter). The results were compared with results using a competitive ligand binding assay, and with effects on forskolin-stimulated cAMP levels (PerkinElmer LANCE). The authors show good correlation between the 3 assay systems tested, with the beta-arrestin protein complementation assay exhibiting a more robust signal than the cAMP assay for cannabinoid CB(2) agonists. Further assay validation shows that DiscoveRx PathHunter HEK293 CB(2) beta-arrestin assay can be carried out from cryopreserved cell suspensions, eliminating variations caused by the need for multiple cell pools during live cell screening campaigns. These results, and the authors' results evaluating a test set of random library compounds, validate the use of ligand-induced interaction between the human cannabinoid CB(2) receptor and beta-arrestin as an appropriate and valuable screening platform for compounds specific for the cannabinoid CB(2) receptor.

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来源期刊

Journal of Biomolecular Screening 生物-分析化学

CiteScore

2.41

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Advancing the Science of Drug Discovery: SLAS Discovery reports how scientists develop and utilize novel technologies and/or approaches to provide and characterize chemical and biological tools to understand and treat human disease. SLAS Discovery is a peer-reviewed journal that publishes scientific reports that enable and improve target validation, evaluate current drug discovery technologies, provide novel research tools, and incorporate research approaches that enhance depth of knowledge and drug discovery success. SLAS Discovery emphasizes scientific and technical advances in target identification/validation (including chemical probes, RNA silencing, gene editing technologies); biomarker discovery; assay development; virtual, medium- or high-throughput screening (biochemical and biological, biophysical, phenotypic, toxicological, ADME); lead generation/optimization; chemical biology; and informatics (data analysis, image analysis, statistics, bio- and chemo-informatics). Review articles on target biology, new paradigms in drug discovery and advances in drug discovery technologies. SLAS Discovery is of particular interest to those involved in analytical chemistry, applied microbiology, automation, biochemistry, bioengineering, biomedical optics, biotechnology, bioinformatics, cell biology, DNA science and technology, genetics, information technology, medicinal chemistry, molecular biology, natural products chemistry, organic chemistry, pharmacology, spectroscopy, and toxicology.