Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM.

Authors :: Sheffler DJ
Wenthur CJ
Bruner JA
Carrington SJ
Vinson PN
Gogi KK
Blobaum AL
Morrison RD
Vamos M
Cosford ND
Stauffer SR
Daniels JS
Niswender CM
Conn PJ
Lindsley CW
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Jun 15; Vol. 22 (12), pp. 3921-5. Date of Electronic Publication: 2012 Apr 30.
Publication Year :: 2012
Abstract: Herein we report the discovery and SAR of a novel metabotropic glutamate receptor 3 (mGlu(3)) NAM probe (ML289) with 15-fold selectivity versus mGlu(2). The mGlu(3) NAM was discovered via a 'molecular switch' from a closely related, potent mGlu(5) positive allosteric modulator (PAM), VU0092273. This NAM (VU0463597, ML289) displays an IC(50) value of 0.66 μM and is inactive against mGlu(5).<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Subjects :: Allosteric Regulation
Cell Line
Central Nervous System drug effects
Central Nervous System metabolism
Drug Discovery
Glutamic Acid metabolism
Humans
Microsomes, Liver metabolism
Molecular Probes pharmacology
Permeability
Piperidines pharmacology
Receptor, Metabotropic Glutamate 5
Sensitivity and Specificity
Structure-Activity Relationship
Microsomes, Liver drug effects
Molecular Probes chemical synthesis
Piperidines chemical synthesis
Receptors, Metabotropic Glutamate antagonists & inhibitors
Receptors, Metabotropic Glutamate metabolism

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