QNZ46

QNZ46 is a highly selective noncompetitive NMDA receptor antagonist targeting GluN2C/D (IC₅₀=3.9 μM), GluN1/GluN2C (IC₅₀=7.1 μM), and GluN1/GluN2D (IC₅₀=182 μM) subunits. QNZ46 inhibits glutamate-mediated calcium influx, thereby blocking excitotoxicity. QNZ46 is membrane permeable and can cross the blood-brain barrier, where it inhibits myelin damage and axonal degeneration^[1][2][3]. In Vitro:Cell viability assay: QNZ46 (1-20 μM; 48 h) significantly reduces neuronal cell viability, and the inhibition rate was positively correlated with the concentration^[2].
Immunofluorescence assay: QNZ46 (50 μM; 2 h) reduces myelin swelling in the myelin injury model and protected structural integrity^[2].
WB assay: QNZ46 (10 μM; 24 h) decreases MLKL phosphorylation and RIP1 expression, may cause suppression of necroptosis pathways^[2]. In Vivo:Ischemic stroke model: QNZ46 (20 mg/kg; i.p.; single administration) significantly reduces brain lesion volume and improved neurological function in transient middle cerebral artery occlusion (tMCAO) mice^[2].
EAE model: QNZ46 (2 mg/kg+1 mg/kg CP465022; i.p.; once a day for 28 days) significantly reduces clinical scores in experimental autoimmune encephalomyelitis (EAE) mice and protected small-diameter myelinated axons in the spinal cord^[3].