Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay
文献类型：期刊论文
| 作者 | Li, Qun-yi1,2; Xu, Ming-kai1,2; Liu, Gang3; Christoffersen, Claus Tornby4; Wang, Ming-wei1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013-08 |
| 卷号 | 34期号:8页码:1116-1120 |
| 关键词 | phosphodiesterase 10 (PDE10) papaverine high-throughput screening psychosis |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.25 |
| 文献子类 | Article |
| 英文摘要 | Aim: To develop a homogeneous assay for high-throughput screening (HTS) of inhibitors of phosphodiesterase 10 (PDE10). Methods: Purified human PDE10 enzyme derived from E coli, [H-3]-cAMP and yttrium silicate microbeads were used to develop an HTS assay based on the scintillation proximity assay (SPA) technology. This method was applied to a large-scale screening campaign against a diverse compound library and subsequent confirmation studies. Preliminary structure-activity relationship (SAR) studies were initiated through limited structural modifications of the hits. Results: The IC50 value of the control compound (papaverine) assessed with the SPA approach was comparable and consistent with that reported in the literature. Signal to background (S/B) ratio and Z' factor of the assay system were evaluated to be 5.24 and 0.71, respectively. In an HTS campaign of 71 360 synthetic and natural compounds, 67 hits displayed reproducible PDE10 inhibition, of which, 8 were chosen as the scaffold for structural modifications and subsequent SAR analysis. Conclusion: The homogeneous PDE10 SPA assay is an efficient and robust tool to screen potential PDE10 inhibitors. Preliminary SAR studies suggest that potent PDE10 inhibitors could be identified and developed through this strategy. |
| WOS关键词 | PHOSPHODIESTERASE 10A INHIBITORS ; SCHIZOPHRENIA ; SYMPTOMS ; DISEASE |
| 资助项目 | H Lundbeck A/S[00000000] ; Ministry of Science and Technology of China[2009ZX09302-001] ; Ministry of Science and Technology of China[2012ZX09304011] ; Ministry of Science and Technology of China[2013ZX09507002] ; Shanghai Science and Technology Development Fund[11DZ2292200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4896749 |
| WOS记录号 | WOS:000322709400017 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277520]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wang, Ming-wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China; 4.H Lundbeck & Co AS, DK-2500 Copenhagen, Denmark |
| 推荐引用方式 GB/T 7714 | Li, Qun-yi,Xu, Ming-kai,Liu, Gang,et al. Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay[J]. ACTA PHARMACOLOGICA SINICA,2013,34(8):1116-1120. |
| APA | Li, Qun-yi,Xu, Ming-kai,Liu, Gang,Christoffersen, Claus Tornby,&Wang, Ming-wei.(2013).Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay.ACTA PHARMACOLOGICA SINICA,34(8),1116-1120. |
| MLA | Li, Qun-yi,et al."Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay".ACTA PHARMACOLOGICA SINICA 34.8(2013):1116-1120. |
入库方式： OAI收割
来源：上海药物研究所
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