Discovery of the First Highly Selective Antagonist of the GluK3 Kainate Receptor Subtype.

ABSTRACT: Kainate receptors belong to the family of glutamate receptors ion channels, which are responsible for the majority of rapid excitatory synaptic transmission in the central nervous system. The therapeutic potential of kainate receptors is still poorly understood, which is also due to the lack of potent and subunit-selective pharmacological tools. In search of selective ligands for the GluK3 kainate receptor subtype, a series of quinoxaline-2,3-dione analogues was synthesized and pharmacologically characterized at selected recombinant ionotropic glutamate receptors. Among them, compound 28 was found to be a competitive GluK3 antagonist with submicromolar affinity and unprecedented high binding selectivity, showing a 400-fold preference for GluK3 over other homomeric receptors GluK1, G

SUBMITTER: Chalupnik P 

PROVIDER: S-EPMC9369419 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature