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Development of a Novel, CNS-penetrant, Metabotropic Glutamate Receptor 3 (mGlu3) NAM Probe (ML289) Derived From a Closely Related mGlu5 PAM

Douglas J Sheffler, Cody J Wenthur, Joshua A Bruner, Sheridan J S Carrington, Paige N Vinson, Kiran K Gogi, Anna L Blobaum, Ryan D Morrison, Mitchell Vamos, Nicholas D P Cosford, Shaun R Stauffer, J Scott Daniels, etc.

Bioorg Med Chem Lett. 2012 Jun 15;22(12):3921-5.

PMID: 22607673

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).

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1382481799 ML289 ML289 1382481-79-9 Price
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