PE859 is a potent inhibitor of both tau and Aβ aggregation with IC50 values of 0.66 and 1.2 μM, respectively.
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 formation of beta-sheet structure[2].
PE859 could cross the blood-brain barrier and that PE859 could be distributed into the tissues of the central nervous system. The maximum concentration of PE859 is 2.005 μg/mL in the blood at 3 h and 1.428 μg/g in the brain at 6 h. PE859 delays onset and progression of the motor dysfunction in JNPL3 mice. PE859 delays progression of the motor dysfunction through the inhibition of accumulation of sarkosyl-insoluble tau. [2]
[1]. Okuda M, et al. Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors. Bioorg Med Chem Lett. 2016 Oct 15;26(20):5024-5028. [2]. Okuda M, et al. PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo. PLoS One. 2015 Feb 6;10(2):e0117511.