VU-0422288(VU-0422288) - 药物靶点：mGluR7_在研适应症：精神障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

mGluR7

作用机制

mGluR7 正变构调节剂(代谢型谷氨酸受体-7 正变构调节剂)

治疗领域

其他疾病

在研适应症

精神障碍

非在研适应症-

原研机构

Vanderbilt University

在研机构

Vanderbilt University

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C17H11Cl2N3O2

InChIKeyMZRLPXFGQKQHST-UHFFFAOYSA-N

CAS号1630936-95-6

关联

100 项与 VU-0422288 相关的临床结果

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100 项与 VU-0422288 相关的转化医学

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100 项与 VU-0422288 相关的专利（医药）

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1

项与 VU-0422288 相关的文献（医药）

2014-12-17·ACS Chemical Neuroscience3区 · 医学

Identification of Positive Allosteric Modulators VU0155094 (ML397) and VU0422288 (ML396) Reveals New Insights into the Biology of Metabotropic Glutamate Receptor 7

3区 · 医学

Article

作者: Darren W. Engers ; Rebecca Klar ; Francine Acher ; Adam G. Walker ; Julie R. Field ; Craig W. Lindsley ; Emily L. Days ; Margrith E. Mattmann ; L. Michelle Lewis ; Karen J. Gregory ; Delphine Rigault ; Colleen M. Niswender ; P. Jeffrey Conn ; Bruce J. Melancon ; Miguel Hurtado ; Rocio Zamorano ; C. David Weaver ; Michael R. Wood ; Corey R. Hopkins ; Thomas J. Utley ; Zixiu Xiang ; Sean R. Bollinger ; Nidhi Jalan-Sakrikar

Metabotropic glutamate receptor 7 (mGlu7) is a member of the group III mGlu receptors (mGlus), encompassed by mGlu4, mGlu6, mGlu7, and mGlu8. mGlu7 is highly expressed in the presynaptic active zones of both excitatory and inhibitory synapses, and activation of the receptor regulates the release of both glutamate and GABA. mGlu7 is thought to be a relevant therapeutic target for a number of neurological and psychiatric disorders, and polymorphisms in the GRM7 gene have been linked to autism, depression, ADHD, and schizophrenia. Here we report two new pan-group III mGlu positive allosteric modulators, VU0155094 and VU0422288, which show differential activity at the various group III mGlus. Additionally, both compounds show probe dependence when assessed in the presence of distinct orthosteric agonists. By pairing studies of these nonselective compounds with a synapse in the hippocampus that expresses only mGlu7, we have validated activity of these compounds in a native tissue setting. These studies provide proof-of-concept evidence that mGlu7 activity can be modulated by positive allosteric modulation, paving the way for future therapeutics development.

100 项与 VU-0422288 相关的药物交易

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