1. Epigenetics
  2. Histone Demethylase
  3. T-448 free base

T-448 free base 

Cat. No.: HY-122635
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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.

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T-448 free base Chemical Structure

T-448 free base Chemical Structure

CAS No. : 1597426-52-2

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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].

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].

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 in the mouse hippocampus.
Resulted in partial but statistically significant and dosedependent rescue effects on the rate of correct choices in NR1-hypo mice.
Molecular Weight

328.43

Formula

C₁₇H₂₀N₄OS

CAS No.

1597426-52-2

SMILES

O=C(NC1=NN=C(C)S1)C2=CC=CC([[email protected]]3[[email protected]](NC4CCC4)C3)=C2

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Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

References
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Keywords:

T-448T448T 448Histone DemethylaseInhibitorinhibitorinhibit

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T-448 free base
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