Delving into the Latest Updates on VU-0422288 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

mGluR7

Mechanism

mGluR7 positive allosteric modulator(Metabotropic glutamate receptor 7 positive allosteric modulator)

Therapeutic Areas

Other Diseases

Active Indication

Psychotic Disorders

Inactive Indication-

Originator Organization

Vanderbilt University

Active Organization

Vanderbilt University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC17H11Cl2N3O2

InChIKeyMZRLPXFGQKQHST-UHFFFAOYSA-N

CAS Registry1630936-95-6

Author: 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 ; Miguel Hurtado ; P. Jeffrey Conn ; Bruce J. Melancon ; Colleen M. Niswender ; Rocio Zamorano ; C. David Weaver ; Michael R. Wood ; Zixiu Xiang ; Thomas J. Utley ; Corey R. Hopkins ; 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 Deals associated with VU-0422288

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