BPN-15606, an orally active γ-secretase modulator (GSM), significantly reduces Aβ42 and Aβ40 production in SHSY5Y neuroblastoma cells, demonstrating IC50 values of 7 nM and 17 nM, respectively. This compound exhibits favorable pharmacokinetic/pharmacodynamic (PK/PD) properties, such as bioavailability, half-life, and clearance. Importantly, BPN-15606 markedly decreases Aβ42 and Aβ40 levels in the central nervous system of both rats and mice[1].

Administered orally at a dosage of 25 mg/kg, BPN-15606 significantly impacts Aβ42 and Aβ40 levels in both the brain and plasma of C57BL/6 mice, showing effects approximately 30–60 minutes after administration and lasting for over 24 hours [1]. When given at dosages of 5 mg/kg, 25 mg/kg, and 50 mg/kg over 9 days, it demonstrates a dose-dependent reduction of Aβ42 and Aβ40 levels in rat CSF [1]. Moreover, administered at 10 mg/kg, 25 mg/kg, and 50 mg/kg for 7 days, BPN-15606 shows remarkable dose-dependent efficacy in lowering Aβ42 and Aβ40 levels in both the plasma and brain of mice [1].