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Updated: May 29, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Structure-activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators
Xuechao Xing1, Ling-Chu Chang, Qiongman Kong
1Laboratory for Drug Discovery in Neurodegeneration, Harvard NeuroDiscovery Center, Brigham & Women's Hospital and Harvard Medical School, 65 Landsdowne St., Cambridge, MA 02139, USA.
Abstract:
Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter and functions to remove glutamate from synapses. A thiopyridazine derivative has been found to increase EAAT2 protein levels in astrocytes. A structure-activity relationship study revealed that several components of the molecule were required for activity, such as the thioether and pyridazine. Modification of the benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that enhanced EAAT2 levels by >6-fold at concentrations < 5 microM after 24h. In addition, one of the derivatives (7-22) enhanced EAAT2 levels 3.5-3.9-fold after 24h with an EC(50) of 0.5 microM.
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