Glutamate is a key excitatory neurotransmitter in the brain, playing a pivotal role in various central nervous system functions, including those related to emotions, cognition, and motor functions. Glutamate receptors can be broadly classified into two major categories: ionotropic iGlu receptors and metabotropic mGlu receptors (see Figure 1). Ionotropic glutamate receptors are ligand-gated ion channels activated by specific ligands like AMPA, Kainate, and NMDA. On the other hand, metabotropic glutamate receptors comprise a family of eight G protein-coupled receptors (GPCRs) that are attractive targets for drug discovery aimed at modulating glutamate-related activities and responses [1]. Notably, recent research has identified metabotropic glutamate receptors as promising candidates for the development of new antidepressant medications [2].
Our cheminformatics team has designed a specialized Glutamate Receptor Screening Compound Library containing over 4,600 small-molecule compounds with drug-like properties to facilitate glutamate receptor-focused drug discovery projects.
One particularly significant subset of glutamatergic receptors, known as NMDA receptors (NMDARs), has been linked to the pathogenesis and progression of neuropsychiatric disorders, such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia. Consequently, they represent potential therapeutic targets for addressing these disorders. At Life Chemicals, we offer a dedicated N-methyl-D-aspartate (NMDA) Receptor Screening Library to support research efforts in this specific area.
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Figure 1. Classification of the glutamate receptors
Compound selection
To compile a reference set of compounds with dose-response activity (IC50, EC50, or Ki, etc.) on glutamate receptors, we initially gathered data from relevant publications and patents. The activity cut-off was set at 10 μM. The selection resulted in the following:
- Metabotropic glutamate (mGlu) receptors: 7,668 reference compounds;
- Ionotropic glutamate receptors (iGlu): 5,982 reference compounds.
Subsequently, we conducted a thorough analysis of the Life Chemicals HTS Compound Collection to identify analogs of known glutamate receptor inhibitors. This analysis was based on a 2D fingerprint similarity search with a Tanimoto cut-off greater than 0.8, using MDL public key fingerprints. This allowed us to generate the subsets for the Glutamate Receptor Focused Library shown below:
- 3,300 potential ligands of metabotropic glutamate receptors;
- 1,300 potential modulators of ionotropic glutamate receptors.
Representative screening compounds from the Glutamate Receptor-focused Screening Library
References:
- Llinas del Torrent, C.; Pérez-Benito, L.; Tresadern, G. Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors. Molecules 2019, 24 (6), 1098.
- Musazzi L. Targeting metabotropic glutamate receptors for rapid-acting antidepressant drug discovery. Expert Opin Drug Discov. 2021 Feb;16(2):147-157. doi: 10.1080/17460441.2020.1822814. Epub 2020 Sep 23. PMID: 32962432.