2. Epigenetics
  3. Histone Demethylase
  4. T-448

T-448 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 enhances H3K4 methylation in primary cultured rat neurons.

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T-448 Chemical Structure

T-448 Chemical Structure

CAS No. : 1597426-53-3

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Based on 1 publication(s) in Google Scholar

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T-448 Related Antibodies

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  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

T-448 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 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

T-448 Related Antibodies

RT-PCR[1].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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

386.50

Formula

C17H20N4OS.1/2C4H4O4
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(NC1=NN=C(C)S1)C2=CC=CC([C@H]3[C@H](NC4CCC4)C3)=C2.O=C(O)/C=C/C(O)=O.[1/2]
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility
In Vitro: 

DMSO : 16.67 mg/mL (43.13 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.5873 mL 12.9366 mL 25.8732 mL
5 mM 0.5175 mL 2.5873 mL 5.1746 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 1.67 mg/mL (4.32 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 1.67 mg/mL (4.32 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 98.86%

COA (251 KB) HNMR (205 KB) LCMS (121 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.5873 mL 12.9366 mL 25.8732 mL 64.6831 mL
5 mM 0.5175 mL 2.5873 mL 5.1746 mL 12.9366 mL
10 mM 0.2587 mL 1.2937 mL 2.5873 mL 6.4683 mL
15 mM 0.1725 mL 0.8624 mL 1.7249 mL 4.3122 mL
20 mM 0.1294 mL 0.6468 mL 1.2937 mL 3.2342 mL
25 mM 0.1035 mL 0.5175 mL 1.0349 mL 2.5873 mL
30 mM 0.0862 mL 0.4312 mL 0.8624 mL 2.1561 mL
40 mM 0.0647 mL 0.3234 mL 0.6468 mL 1.6171 mL
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T-448 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

T-4481597426-53-3T448T 448Histone DemethylaseInhibitorinhibitorinhibit

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