Francine Acher - Université Paris Descartes

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Contact : andre.klarsfeld@espci.fr

15 mars 2012 11:30 » 13:30 — Amphithéâtre Urbain

Metabotropic glutamate receptors : drug discovery and mechanism investigations

Glutamate is the major excitatory neurotransmitter in the central nervous
system (CNS) and activates two types of receptors : the ionotropic glutamate
receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs). The latter are perceived as very promising therapeutic targets for various CNS diseases because of their modulatory role in synaptic transmission. Indeed less side effects are expected with pharmacological intervention at mGluRs in comparaison to iGluRs. The presentation will focus on the two approaches (rational design and virtual high throughput screening) that we developed in order to discover new agonists of subtype4 of mGluRs. I will show how 3D-models were used to investigate the receptor activation mechanism and how potent and selective ligands were found and tested in vitro as well as in animal models of Parkinson’s disease or inflammatory pain.

References :

Goudet et al. FASEB J. 2012 Jan 5. [Epub ahead of print] ; Selvam et al. JMedChem

2010, 53, 2797 ; Beurrier et al. FASEB J. 2009, 23, 3619.

For a complete publication list, click here

Ce séminaire est proposé conjointement par le laboratoire de Chimie organique et le laboratoire de Neurobiologie





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