FP802 is a potent oral TwinF interface inhibitor capable of disrupting and neutralizing the toxicity of the NMDAR/TRPM4 death complex. Within the 5xFAD Alzheimer's disease (AD) mouse model, FP802 demonstrates significant neuroprotective effects, preventing cognitive decline, preserving neuronal structural integrity, reducing β-amyloid plaque formation, and mitigating mitochondrial damage. In the amyotrophic lateral sclerosis (ALS) mouse model, FP802 prevents motor neuron loss, lowers serum neurofilament light chain (NfL) levels, improves motor performance, and extends the lifespan of mice. FP802 can be utilized for research related to Alzheimer's disease and amyotrophic lateral sclerosis [1][2].

FP802, at a concentration of 8 μM over 24-72 hours, effectively disrupts the NMDAR/TRPM4 complex, offering neuroprotection in cellular models without directly promoting or inhibiting neurite growth. When used at 10 μM for 30 minutes, FP802 provides significant neuroprotection against glutamate (20 μM)-mediated toxicity, with an IC50 of 8.7 μM, and restores NMDA-inhibited immediate early gene expression to physiological levels. In HEK293 cells, FP802 does not exhibit antagonistic activity against NMDAR (GluN1/GluN2A and GluN1/GluN2B) as the IC50 values are both greater than 250 mM. Additionally, FP802, applied for 30 minutes, can dose-dependently block post-mitotic cell death of neurons in NMDA-induced sporadic ALS-specific induced pluripotent stem cell (iPSC)-derived forebrain organoids.

FP802, when administered orally at doses of 10 and 40 mg/kg once daily for 4 months, enhances cognitive function, prevents neuronal structural decay, and reduces amyloid pathology in 5xFAD mice. Additionally, subcutaneous administration of FP802 at 40 mg/kg, once daily starting around week 15 for 4 weeks, safely protects against motor neuron degeneration and extends survival in ALS mice by targeting the NMDAR/TRPM4 complex.