Biological Activity
Compound 8 (C8) is a small molecule th at directly targets TRPM4 TwinF domain and blocks its interaction with GluN2A/GluN2B (NR2A/NR2B) I4 domain. C8 prevents NMDAR/TRPM4 interaction-dependent excitotoxicity (death protection EC50 = 2.1 μM 24 h post 10-min exposure of primary murine hippocampal neurons to 20 μM NMDA) without affecting, and even enhancing, NMDAR-mediated essential functions. C8 protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell (RGC) loss in mice in vivo (40 mg/kg i.p. at -16h, -3h before, 0h, 3h, 24h after MCAO or 20 nmol NMDA/2.0 μL by intravitreal injection).