Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu 3) NAM probe (ML289) derived from a closely related mGlu 5 PAM

…, JA Bruner, SJS Carrington, PN Vinson, KK Gogi…

Index: Sheffler, Douglas J.; Wenthur, Cody J.; Bruner, Joshua A.; Carrington, Sheridan J.S.; Vinson, Paige N.; Gogi, Kiran K.; Blobaum, Anna L.; Morrison, Ryan D.; Vamos, Mitchell; Cosford, Nicholas D.P.; Stauffer, Shaun R.; Scott Daniels; Niswender, Colleen M.; Jeffrey Conn; Lindsley, Craig W. Bioorganic and Medicinal Chemistry Letters, 2012 ,  vol. 22,  # 12  p. 3921 - 3925

Full Text: HTML

Citation Number: 20

Abstract

Herein we report the discovery and SAR of a novel metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) with 15-fold selectivity versus mGlu2. The mGlu3 NAM was discovered via a 'molecular switch'from a closely related, potent mGlu5 positive allosteric modulator (PAM), VU0092273. This NAM (VU0463597, ML289) displays an IC50 value of 0.66 μM and is inactive against mGlu5.