2. Academic Validation
  3. Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators

Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators

  • J Med Chem. 2010 Dec 23;53(24):8775-9. doi: 10.1021/jm101069m.
Stephan Schann 1,  Stanislas Mayer,  Christel Franchet,  Mélanie Frauli,  Edith Steinberg,  Mireille Thomas,  Luc Baron,  Pascal Neuville
Affiliations

Affiliation

  • 1 Domain Therapeutics SA, Bioparc, Boulevard Sebastien Brant, F-67400 Strasbourg-Illkirch, France. sschann@domaintherapeutics
PMID: 21105727 DOI: 10.1021/jm101069m
Abstract

Using an mGluR2 FRET-based binding assay, binders of the transmembrane region devoid of functional activity were identified. It is reported that slight chemical modifications of these SAMs can dramatically change activity of the resulting analogues without altering their affinities. Starting from compound 1, three mGluR2 NAMs showing also mGluR3 PAM activities were obtained. SAMs therefore represent a useful approach to explore the chemical space for GPCR allosteric modulator identification.

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