1597426-52-2

1597426-52-2 structure

Name: T-448 free base
Chemical Name: T-448 free base
CAS Number: 1597426-52-2
Molecular Formula: C₁₇H₂₀N₄OS
Molecular Weight: 328.434
Catalog: Signaling Pathways Epigenetics Histone Demethylase
Create Date: 2019-09-09 22:10:48
Modify Date: 2024-01-14 17:06:21
T-448 free base is a specific, orally active 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].

Name	T-448 free base
Synonyms	3-((1S,2R)-2-(cyclobutylamino)cyclopropyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide

Description	T-448 free base is a specific, orally active 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].
Related Catalog	Signaling Pathways >> Epigenetics >> Histone Demethylase Research Areas >> Neurological Disease
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]. Cell Viability Assay 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[1]. T-448 increases H3K4 methylation in the brain without causing hematological side effects even at 100 mg/kg[1]. Animal Model: NR1-hypo mice[1]. Dosage: 1, 10 mg/kg. Administration: Orally, 3 weeks. Result: Dose-dependently increased the H3K4me2 levels around Bdnf, Arc, and Fos genes inthe mouse hippocampus. Resulted in partial but statistically significant and dosedependent rescue effects on the rate of correct choices in NR1-hypo mice.
References	[1]. Matsuda S, et al. T-448, a specific inhibitor of LSD1 enzyme activity, improves learning function without causing thrombocytopenia in mice. Neuropsychopharmacology. 2018 Dec 22.

Molecular Formula	C₁₇H₂₀N₄OS
Molecular Weight	328.434

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