KDS12025 is a specific, BBB-permeable small molecule that enhances hemoglobin (Hb) pseudoperoxidase activity 100-fold (EC50=0.04 uM), enabling effective H2O2 decomposition even at extremely low Hb levels.
KDS12025 does not degrade H2O2 without Hb, and not affect other peroxidases.
KDS12025 also exhibits efficacy comparable to that of mouse Hb.
KDS12025 decreased Hb EC50 for H2O2 decomposition by 4.7-fold and EC20 by 98-fold.
KDS12025 potently enhances Hb pseudoperoxidase activity without altering its respiratory function or metabolism in mice.
KDS12025 effectively reduces AD- and PD-like pathology in vitro, KDS12025 (10 μM) significantly reduced Aβ-induced H2O2 with an EC50 of 0.5 μM.
KDS12025 effectively mitigates Aβ-, MAOB-, and 6-OHDA-associated H2O2 levels in cultured astrocytes.
KDS12025 (3 mg/kg/day (mpk)) significantly improved memory impairment, restored astrogliosis, and normalized aberrant tonic GABA currents in APP/PS1 mouse model.
KDS12025 effectively and potently reverses key AD pathological features, including neurodegeneration, astrogliosis, oxidative stress, and memory impairment.