Development of a complex scintillation proximity assay for high-throughput screening of ppar gamma modulators
文献类型：期刊论文
| 作者 | Wu, B; Gao, J; Wang, MW |
| 刊名 | Acta pharmacologica sinica
 |
| 出版日期 | 2005-03-01 |
| 卷号 | 26期号:3页码:339-344 |
| 关键词 | Peroxisome proliferator-activated receptor gamma Retinoid x receptor alpha Scintillation proximity assay High-throughput screening |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2005.00040.x |
| 通讯作者 | Wang, mw(mwwang@siniwest.com) |
| 英文摘要 | Aim: to develop a complex high-throughput screening (hts) assay based on scintillation proximity assay (spa) technology for identification of novel peroxisome proliferator-activated receptor gamma (ppar gamma) modulators. methods: full-length ppar gamma and retinoid x receptor alpha (rxr alpha), biotinylated ppar response element (ppre), [(3)h]brl49653 and streptavidin-coated flashplate or microbead were used to develop an hts assay based on spa technology. this 'abcde' method was validated against conventional hydroxyapatite (ha) assay and applied to large-scale screening of 16 000 synthetic compounds and natural product extracts. results: (1) ic(50) values of positive control compounds (brl49653 and troglitazone) obtained from the 'abcde' method and ha assay were comparable and consistent with those reported elsewhere; (2) approximately 178 showing more than 70% competitive inhibition on brl49653 binding to ppary, were identified initially by the 'abcde' method (microbead); (3) secondary screening using flashplate and cross-reactivity studies with rar alpha, beta, gamma and rxr alpha, beta, gamma confirmed that 12 compounds possessed specific ppary binding properties including 2 with ic(50) values less than 0.5 mu mol/l and novel chemical structures. conclusions: the 'abcde' method using either flashplate or microbead, is a highly efficient, automatable, and robust tool to screen potential ppary modulators in hts setting. its application may be expanded to other nuclear receptors that form heterodimers upon activation. |
| WOS关键词 | PROLIFERATOR-ACTIVATED RECEPTOR ; RETINOID-X-RECEPTOR ; PEROXISOME-PROLIFERATOR ; BINDING ; SUPERFAMILY ; DNA |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| WOS类目 | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000227647800013 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2376972 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Wang, MW |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, B,Gao, J,Wang, MW. Development of a complex scintillation proximity assay for high-throughput screening of ppar gamma modulators[J]. Acta pharmacologica sinica,2005,26(3):339-344. |
| APA | Wu, B,Gao, J,&Wang, MW.(2005).Development of a complex scintillation proximity assay for high-throughput screening of ppar gamma modulators.Acta pharmacologica sinica,26(3),339-344. |
| MLA | Wu, B,et al."Development of a complex scintillation proximity assay for high-throughput screening of ppar gamma modulators".Acta pharmacologica sinica 26.3(2005):339-344. |
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来源：中国科学院大学
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