T-448

T-448 is a specific, orally active and irreversible inhibitor of lysine-specific demethylase 1 (LSD1, an H3K4 demethylase) , with an IC 50 of 22 nM. T-448 enhances H3K4 methylation in primary cultured rat neurons 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. RT-PCR. Cell Line: Primary cultured rat neurons. Concentration: 0-10 μM. Incubation Time: 1 day treatment. Result: Increased Ucp2 H3K4me2 and Ucp2 mRNA significantly. 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 . T-448 increases H3K4 methylation in the brain without causing hematological side effects even at 100 mg/kg . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NR1-hypo mice . Dosage: 1, 10 mg/kg. Administration: Orally, 3 weeks. Result: Dose-dependently increased the H3K4me2 levels around Bdnf, Arc, and Fos genes in the mouse hippocampus. Resulted in partial but statistically significant and dosedependent rescue effects on the rate of correct choices in NR1-hypo mice. Form:Solid IC50& Target:IC50: 22 nM (LSD1)

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