YB-537 (YB537) is a potent, highly specific quinone reductase 2 (QR2) inhibitor with IC50 of 3 nM, shows no activity against QR1 (IC50>10 uM).
YB-537 binds to the catalytic site through a series of hydrophobic and hydrogen bonds with both FAD and amino acids from both QR2 monomers.
YB-537 can bind native QR2 in human cells and replicate the effects seen using genetic QR2 removal.
YB-537 enhances cortical and hippocampal learning in mice and rats.
YB-537 (50 mg/kg, in drinking water) improves cognitive function in 9- month-old 5xFAD female mice.
YB-537 reduces metabolic burden and reverses Alzheimer's disease phenotype in mice.
