PE859 is a potent inhibitor of both tau and Aβ aggregation.

β-Amyloid:1.2 μM, Tau:0.66 μM

在阿尔茨海默症患者的大脑中，老年斑和神经纤维缠结作为这一疾病的两大标志性特征被观察到，它们是由淀粉样β (Aβ) 肽和Tau蛋白的异常聚集形成的。PE859以浓度依赖性的方式抑制了肝素诱导的3RMBD和Tau全长的聚集。在每项测定中，最后测量周期计算的IC50值分别为0.81 μM和2.23 μM。PE859通过形成β-折叠结构抑制Tau聚集[2]。

PE859能够穿越血脑屏障，因此能分布到中央神经系统的组织中。PE859在血液中的最大浓度在3小时达到2.005 μg/mL，而在6小时达到脑部的1.428 μg/g。PE859延缓了JNPL3小鼠运动功能障碍的发生和进展，这种延缓是通过抑制sarkosyl-insoluble tau的积累来实现的。[2]

PEL cells are incubated in triplicate in a 96-well microculture plate in the presence of different concentrations of methyl-β-cyclodextrin (0-10 mM) in a final volume of 0.1 mL for 24 h at 37°C. Subsequently, MTT (0.5 mg/mL final concentration) is added to each well. After 3 h of additional incubation, 100 μL of a 0.04 N HCl is added to dissolve the crystals. Absorption values at 570 nm are determined.