| References: |
FPS-ZM1 is a blood-brain-barrier-permeant, non-toxic, tertiary amide compound that acts as a high affinity, potent, multimodal blocker of RAGE (Receptor for Advanced Glycation End products) V domain-mediated ligand binding (Ki = 25, 148, and 230 nM, respectively, against Aβ40, HMGB1, and S100B, binding to sRAGE). Blocks RAGE-mediated influx of Aβ40 and Aβ42 into the brain. Also shown to suppress Aβ-RAGE induced NF-κB activation and NF-κB-dependent transcription of β-secretase. Daily treatment of APPsw/0 murine AD model (1 mg/kg/d via i.p.) is reported to greatly reduce Thioflavin S-positive amyloid plaques in cortex and hippocampus (by 70 to 80%) and restore congnitive performance to the level of non-AD mice. |
