T-448 (free base)

T-448 free base is a specific, orally active, CNS-penetrant and irreversible inhibitor of lysine-specific demethylase 1 (LSD1, an H3K4 demethylase), with an IC₅₀ of 22 nM. T-448 free base enhances H3K4 methylation in primary cultured rat neurons^[1]. IC50 & Target:IC50: 22 nM (LSD1)^[1]. In Vitro:T-448 enhances the levels of H3K4 methylation, increased mRNA expression of neural plasticity-related genes including brain derived neurotrophic factor (Bdnf), and ameliorated learning dysfunction^[1]. In Vivo:T-448 has minimal impact on the LSD1-GFI1B complex and a superior hematological safety profile in mice via the generation of a compact formyl-FAD adduct. T-448 increases brain H3K4 methylation and partially restored learning function in mice with NMDA receptor hypofunction^[1].
T-448 increases H3K4 methylation in the brain without causing hematological side effects even at 100 mg/kg^[1].