FP802 is a potent neuroprotectant and small molecule inhibitor of TwinF interface, shows selective elimination of eNMDAR-mediated toxicity via disruption of the NMDAR/TRPM4 death signaling complex, while sparing the vital physiological functions of synaptic NMDARs.
FP802 displays potent protective activity against glutamate-mediated neurotoxicity with IC50 of 8.7 uM for analysis of the percentage of nuclear mCherry-positive neurons.
FP802 eliminates the transcriptional shut-off induced by eNMDARs and boosts the NMDA bath application-induced expression of the immediate-early genes (IEGs) Atf3, Arc, Bdnf, cFos, Inhibin beta A, and Npas4.
FP802 does not not block NMDARs expressed heterologously in HEK293 cells (IC50 > 250 μM for both, GluN1/GluN2A and GluN1/GluN2B).
FP802 (40 mg/kg/day) improves motor performances, extends lifespan, and prevents motor neuron loss in SOD1G93A mice.
FP802 protects human brain organoids generated using iPSCs from ALS patients or healthy controls against NMDA-induced neurotoxicity.