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

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

  • Bioorg Med Chem Lett. 2012 Jun 15;22(12):3921-5. doi: 10.1016/j.bmcl.2012.04.112.
Douglas J Sheffler 1,  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,  Colleen M Niswender,  P Jeffrey Conn,  Craig W Lindsley
Affiliations

Affiliation

  • 1 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
PMID: 22607673 DOI: 10.1016/j.bmcl.2012.04.112
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).

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