T-3775440 hydrochloride

Name: T-3775440 hydrochloride
Brand: MedChemExpress
SKU: HY-103085
Rating: 5.0 (2 reviews)

Cat. No.: HY-103085 Purity: 99.13%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

T-3775440 (hydrochloride) is an irreversible lysine-specific histone demethylase (LSD1) inhibitor with an IC₅₀ value of 2.1 nM.

For research use only. We do not sell to patients.

T-3775440 hydrochloride Chemical Structure

CAS No. : 1422535-52-1

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 286	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 286	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 260	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 390	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 702	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 982	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1374	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 2 publication(s) in Google Scholar

2 Publications Citing Use of MCE T-3775440 hydrochloride

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KDM1/LSD1 KDM2 KDM3 KDM4 KDM5 KDM6

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

T-3775440 (hydrochloride) is an irreversible lysine-specific histone demethylase (LSD1) inhibitor with an IC₅₀ value of 2.1 nM.

IC₅₀ & Target

IC50: 2.1 nM (LSD1)^[1].

In Vitro

T-3775440 demonstrates irreversible inhibition of recombinant human LSD1, with a kinact/KI value of 1.7×10⁵ (sec⁻¹ M⁻¹). T-3775440 is highly selective for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B), with an IC₅₀ value of 2.1 nM). T-3775440 blocks the proliferation of several cell lines as quickly as day 3 of treatment. Notably, the granulocyte/macrophage markers CD86 and CD11b are commonly upregulated on both TF-1a and HEL92.1.7 cells in response to T-3775440 treatment, whereas the erythroid markers CD235a and CD71 are downregulated by this treatment. In CMK11-5 cells, CD86 mRNA expression is also clearly upregulated by T-3775440 in a concentration-dependent manner, although only a modest increase in cell surface CD86 expression is observed. T-3775440 treatment disrupts the LSD1-GFI1B association in a concentration-dependent manner. T-3775440 decreases LSD1 binding but not GFI1B binding and increases the level of dimethylated H3K4 at the PI16 locus^[1].

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

In Vivo

T-3775440 upregulates CD86 mRNA expression in tumor xenografts of HEL92.1.7 cells in a dose-dependent manner following the oral administration of single doses ranging from 3 to 30 mg/kg. To investigate target engagement of this compound in tumors, PI16 expression levels is tested as a direct biomarker. As expected, PI16 suppression is dramatically reversed by T-3775440 treatment. In a TF-1a (AEL) tumor xenograft model, T-3775440 exhibits significant antitumor effects, with 15-day T/C values of 15.6% and <0% at doses of 20 and 40 mg/kg, respectively. T-3775440 also exhibits potent antitumor effects in an additional AEL model of HEL 92.1.7 and an AMKL model of CMK11-5, leading to nearly complete tumor growth suppression during the dosing period. It is found that in mice, T-3775440 treatment results in a transient reduction in platelets, followed by a significant rebound; this is considered a mechanism-based adverse effect of LSD1 inhibition. On a dosing schedule comprising 5 days on/2 days off, a statistically significant difference in body weight is observed between vehicle- and T-3775440–treated tumor xenograft model mice at higher doses. However, efficacious T-3775440 doses are tolerated in all subcutaneous tumor xenograft models^[1].

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

Molecular Weight

346.85

Formula

C₁₈H₂₃ClN₄O

CAS No.

1422535-52-1

Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(NC1=CC=C([C@@H]2C[C@H]2NCC3CC3)C=C1)C4=CN(C)N=C4.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, stored under nitrogen, away from moisture

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

Solvent & Solubility

In Vitro:

DMSO : ≥ 30.18 mg/mL (87.01 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 8.33 mg/mL (24.02 mM; ultrasonic and warming and heat to 60°C)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.8831 mL	14.4155 mL	28.8309 mL
5 mM	0.5766 mL	2.8831 mL	5.7662 mL
10 mM	0.2883 mL	1.4415 mL	2.8831 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, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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: ≥ 2.5 mg/mL (7.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (7.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (7.21 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

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, away from moisture)

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: 99.13%

Select Batch:

Data Sheet (278 KB) SDS (252 KB)

COA (247 KB) HNMR (228 KB) LCMS (134 KB)

Handling Instructions (2659 KB)

References

[1]. Ishikawa Y, et al. A Novel LSD1 Inhibitor T-3775440 Disrupts GFI1B-Containing Complex Leading to Transdifferentiation and Impaired Growth of AML Cells. Mol Cancer Ther. 2017 Feb;16(2):273-284. [Content Brief]

Cell Assay ^[1]	The human leukemia cell lines TF-1a, HEL92.1.7, CMK11-5 and M07e are used. All cells are grown in RPMI1640 plus 10% FBS and maintained in a humidified incubator at 37°C and 5% CO₂. To assess cell proliferation and viability in human leukemia cell lines, compounds (e.g T-3775440) are added with different concentrations (T-3775440: 0, 10, 50 nM) at 24 h after cell seeding. After the incubation period, cells are lysed with CellTiter-Glo, and luminescent signals are detected using an ARVO MX1420 microplate reader. For cell-cycle analysis, cells are fixed overnight with 70% ethanol. Fixed cells are stained with propidium iodide and analyzed on a FACSCalibur or FACSVerse flow cytometer^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	Mice^[1] Female C.B17/Icr-scid/scid Jcl mice are used and maintained under specific pathogen-free conditions. AML cells (2×10⁶ cells) in Matrigel are inoculated subcutaneously into the left flanks of 6- to 7-week-old mice (day 0). Mice are randomized when the mean tumor volume reached approximately 150 to 350 mm³. Subsequently, mice are administrated with vehicle or T-3775440 single doses ranging from 3 to 30 mg/kg once daily on 5 days on/2 days off schedule for 2 weeks. Twice weekly, tumors are measured with vernier calipers, and tumor volumes are calculated^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Ishikawa Y, et al. A Novel LSD1 Inhibitor T-3775440 Disrupts GFI1B-Containing Complex Leading to Transdifferentiation and Impaired Growth of AML Cells. Mol Cancer Ther. 2017 Feb;16(2):273-284. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	2.8831 mL	14.4155 mL	28.8309 mL	72.0773 mL
	5 mM	0.5766 mL	2.8831 mL	5.7662 mL	14.4155 mL
	10 mM	0.2883 mL	1.4415 mL	2.8831 mL	7.2077 mL
	15 mM	0.1922 mL	0.9610 mL	1.9221 mL	4.8052 mL
	20 mM	0.1442 mL	0.7208 mL	1.4415 mL	3.6039 mL
DMSO	25 mM	0.1153 mL	0.5766 mL	1.1532 mL	2.8831 mL
	30 mM	0.0961 mL	0.4805 mL	0.9610 mL	2.4026 mL
	40 mM	0.0721 mL	0.3604 mL	0.7208 mL	1.8019 mL
	50 mM	0.0577 mL	0.2883 mL	0.5766 mL	1.4415 mL
	60 mM	0.0481 mL	0.2403 mL	0.4805 mL	1.2013 mL
	80 mM	0.0360 mL	0.1802 mL	0.3604 mL	0.9010 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.