JNJ-61432059 is a potent, TARPγ-8 selective AMPAR negative modulator with pIC50 of 9.7 in FLIPR assay using HEK-293 cells expressing human GluA1o-γ-8.
JNJ-61432059 does not inhibit glutamate-induced calcium-flux in heterologous cells that coexpressed AMPARs with any TARP other than γ-8 at 10 uM.
JNJ-61432059 also shows no activity against a panel of 52 receptors, ion channels, and transporters using radioligand displacement assays.
JNJ-61432059 demonstrates robust target engagement observed in vivo, shows protection in the corneal kindling model with ED50 of 1.3 mg/kg.
JNJ-61432059 (5 mg/kg, p.o.) demonstrates anticonvulsant efficacy and seizure protection in corneal kindling and pentylenetetrazole (PTZ) anticonvulsant models.
