Chemical Switch of a Metabotropic Glutamate Receptor 2 Silent Allosteric Modulator into Dual Metabotropic Glutamate Receptor 2/3 Negative/Positive Allosteric Modulators
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- 作者：Stephan Schann ; Stanislas Mayer ; Christel Franchet ; Mlanie Frauli ; Edith Steinberg ; Mireille Thomas ; Luc Baron ; Pascal Neuville
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：December 23, 2010
- 年：2010
- 卷：53
- 期：24
- 页码：8775-8779
- 全文大小：770K
- 年卷期：v.53,no.24(December 23, 2010)
- ISSN：1520-4804
文摘
Using an mGluR2 FRET-based binding assay, binders of the transmembrane region devoid of functional activity were identified. It is reported that slight chemical modifications of these SAMs can dramatically change activity of the resulting analogues without altering their affinities. Starting from compound 1, three mGluR2 NAMs showing also mGluR3 PAM activities were obtained. SAMs therefore represent a useful approach to explore the chemical space for GPCR allosteric modulator identification.