Enzyme inhibitor
This orally bioavailable tau aggregation inhibitor (FW = 448.53 g/mol; IUPAC: 3-[(1E)-2-(1H-indol-6-yl)ethenyl]-5-[(1E)-2-[2-methoxy-4-(2- pyridylmethoxy)phenyl]ethenyl]-1H-pyrazole) significantly reduces formation of sarkosyl-insoluble aggregates of Tau, the principal axonal microtubule-associated protein, and prevents onset and progression of the motor dysfunction in JNPL3 Pro-301-Leu-mutated human tau transgenic mice. PE859 also inhibits aggregation of three-repeat Tau, or 3RMBD-Tau (IC50 = 0.81 μM), and four-repeat Tau, or 2N4R-Tau (IC50 = 2.23 μM).
