Positive allosteric modulators to peptide GPCRs: a promising class of drugs
文献类型：期刊论文
| 作者 | Bartfai, Tamas2; Wang, Ming-wei1,3
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2013-07 |
| 卷号 | 34期号:7页码:880-885 |
| 关键词 | neuropeptide galanin GPCR allosteric mudulation CYM2503 anticonvulsant drug screening |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.20 |
| 文献子类 | Review |
| 英文摘要 | The task of finding selective and stable peptide receptor agonists with low molecular weight, desirable pharmacokinetic properties and penetrable to the blood-brain barrier has proven too difficult for many highly coveted drug targets, including receptors for endothelin, vasoactive intestinal peptide and galanin. These receptors and ligand-gated ion channels activated by structurally simple agonists such as glutamate, glycine and GABA present such a narrow chemical space that the design of subtype-selective molecules capable of distinguishing a dozen of glutamate and GABA receptor subtypes and possessing desirable pharmacokinetic properties has also been problematic. In contrast, the pharmaceutical industry demonstrates a remarkable success in developing 1,4-benzodiazepines, positive allosteric modulators (PMAs) of the GABA(A) receptor. They were synthesized over 50 years ago and discovered to have anxiolytic potential through an in vivo assay. As exemplified by Librium, Valium and Dormicum, these allosteric ligands of the receptor became the world's first blockbuster drugs. Through molecular manipulation over the past 2 decades, including mutations and knockouts of the endogenous ligands or their receptors, and by in-depth physiological and pharmacological studies, more peptide and glutamate receptors have become well-validated drug targets for which an agonist is sought. In such cases, the pursuit for PAMs has also intensified, and a working paradigm to identify drug candidates that are designed as PAMs has emerged. This review, which focuses on the general principles of finding PAMs of peptide receptors in the 21st century, describes the workflow and some of its resulting compounds such as PAMs of galanin receptor 2 that act as potent anticonvulsant agents. |
| WOS关键词 | PROTEIN-COUPLED RECEPTORS ; HUMAN GALANIN RECEPTOR ; METABOTROPIC GLUTAMATE RECEPTORS ; ASPARTATE TRANSCARBAMYLASE ; FUNCTIONAL SELECTIVITY ; TYPE-2 RECEPTORS ; LIGAND-BINDING ; MONOD-WYMAN ; AGONIST ; MODEL |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4874881 |
| WOS记录号 | WOS:000321332700003 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277554]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Bartfai, Tamas |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Bartfai, Tamas,Wang, Ming-wei. Positive allosteric modulators to peptide GPCRs: a promising class of drugs[J]. ACTA PHARMACOLOGICA SINICA,2013,34(7):880-885. |
| APA | Bartfai, Tamas,&Wang, Ming-wei.(2013).Positive allosteric modulators to peptide GPCRs: a promising class of drugs.ACTA PHARMACOLOGICA SINICA,34(7),880-885. |
| MLA | Bartfai, Tamas,et al."Positive allosteric modulators to peptide GPCRs: a promising class of drugs".ACTA PHARMACOLOGICA SINICA 34.7(2013):880-885. |
入库方式： OAI收割
来源：上海药物研究所
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