| http://purl.uniprot.org/citations/26919761 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26919761 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26919761 | http://www.w3.org/2000/01/rdf-schema#comment | "The N-methyl-D-aspartate receptor (NMDAR) is a Na(+) and Ca(2+) permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate. NMDARs are critical to synaptic signaling and plasticity, and their dysfunction has been implicated in a number of neurological disorders, including schizophrenia, depression, and Alzheimer's disease. Herein we describe the discovery of potent GluN2A-selective NMDAR positive allosteric modulators (PAMs) starting from a high-throughput screening hit. Using structure-based design, we sought to increase potency at the GluN2A subtype, while improving selectivity against related α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The structure-activity relationship of channel deactivation kinetics was studied using a combination of electrophysiology and protein crystallography. Effective incorporation of these strategies resulted in the discovery of GNE-0723 (46), a highly potent and brain penetrant GluN2A-selective NMDAR PAM suitable for in vivo characterization."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.org/dc/terms/identifier | "doi:10.1021/acs.jmedchem.5b02010"xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.org/dc/terms/identifier | "doi:10.1021/acs.jmedchem.5b02010"xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Fu Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Fu Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Jiang Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Jiang Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu M."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu M."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Luo X."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Luo X."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Lu A."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Lu A."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu Y.'"xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Liu Y.'"xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Wu G."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Wu G."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Sun L."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Sun L."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |
| http://purl.uniprot.org/citations/26919761 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |