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

β-Amyloid:1.2 μM, Tau:0.66 μM

In an Alzheimer's patient's brain, senile plaques and neurofibrillary tangles, the abnormal aggregates of amyloid β (Aβ) peptide and Tau Protein, are observed as the two major hallmarks of this disease. PE859 inhibits the heparin-induced aggregation of both 3RMBD and full length tau in a concentration-dependent manner. In each assay, the IC50 values calculated at the last measurement periods are 0.81 μM, and 2.23 μM, respectively. PE859 inhibits tau aggregation through the formation of a beta-sheet structure[2].

PE859 effectively crosses the blood-brain barrier, enabling its distribution within central nervous system tissues. It reaches a peak concentration of 2.005 μg/mL in blood at 3 hours and 1.428 μg/g in the brain by 6 hours. Notably, PE859 postpones the onset and advancement of motor dysfunction in JNPL3 mice by inhibiting the buildup of sarkosyl-insoluble tau. [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.