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  3. MT-228

MT-228 (BPN-0026709) is a selective and blood-brain barrier permeable non-muscle myosin II inhibitor. MT-228 markedly improves tolerability by selectively targeting NMIIB (KI = 1.5 μM) over CMII (KI = 17 μM), and the sequence of SmMll MD is 83.6% identical to that of NMllB. MT-228 shows long-lasting efficacy in animal models of stimulant use disorder.

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MT-228

MT-228 Chemical Structure

CAS No. : 2404652-24-8

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Description

MT-228 (BPN-0026709) is a selective and blood-brain barrier permeable non-muscle myosin II inhibitor. MT-228 markedly improves tolerability by selectively targeting NMIIB (KI = 1.5 μM) over CMII (KI = 17 μM), and the sequence of SmMll MD is 83.6% identical to that of NMllB. MT-228 shows long-lasting efficacy in animal models of stimulant use disorder[1].

In Vitro

MT-228 (10-3-100 μM) shows improved cardiac safety and selectivity compared to Blebbistatin (HY-13813) with a KINMIIB of 1.5 μM in an ATPase assay[1].
MT-228 shows excellent agreement with the cytokinesis (EC50 = 1.0 μM)[1].

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

Parmacokinetics
Species Dose Route T1/2 Cmax AUClast
Mice[1] 2 mg/kg i.p. 1.8 h 41.5 ng/mL 52 ng·h/mL
Rat[1] 0.5 mg/kg i.v. 1.8 h 91.9 ng/mL 57 ng·h/mL
Rat[1] 2 mg/kg i.v. 3.8 h 533.5 ng/mL 289 ng·h/mL
In Vivo

MT 228 (5-10 mg/kg, i.p., single dose) is well-tolerated up to at least 10 mg/kg in mice[1].
MT-228 (0.5-5 mg/kg, i.p. or i.v., single dose) disrupts the motivation for stimulant in mice and rats[1].

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

Animal Model: 8-10-week-old male C57BL/6 mice (25-30 g)[1]
Dosage: i.p. for a single dose
Administration: 5, 7.5, 10 mg/kg
Result: Showed no significant effects on distance travelled over the first 10 minutes or entire 40 minutes test period post-injection.
Showed no effect on velocity and no difference between time spent in the center versus the sides of the open field.
Animal Model: 8-10-week-old male C57BL/6 mice (25-30 g)[1]
Dosage: i.p. for a single dose
Administration: 0.5, 1, 2.5, 5 mg/kg
Result: Disrupted the motivation for METH at doses as low as 0.5 mg/kg.
Had no effect on a strong preference for the COC-paired chamber (5 mg/kg).
Had no effect on any measure in elevated plus maze, including the total distance travelled in the maze, latency to enter the open (unprotected) arm, or time spent in the open arm(5 mg/kg).
Animal Model: Adult male 250-300 g rats[1]
Dosage: i.v. for a single dose 30 minutes before testing
Administration: 1 mg/kg
Result: Reduced the robust lever pressing displayed by rats.
Removed the motivation to seek METH for at least one month.
Molecular Weight

337.37

Formula

C19H19N3O3

CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C1[C@@]2(O)C(N(C3=CC(OC)=NC=C3)CC2)=NC4=C1C=C(C)C(C)=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 8.33 mg/mL (24.69 mM; ultrasonic and warming and heat to 60°C; 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 2.9641 mL 14.8205 mL 29.6410 mL
5 mM 0.5928 mL 2.9641 mL 5.9282 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

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

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

This equation is commonly abbreviated as: C1V1 = C2V2

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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: ≥ 0.83 mg/mL (2.46 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 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: ≥ 0.83 mg/mL (2.46 mM); Clear solution

    This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 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:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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+
%
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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).
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
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. 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 2.9641 mL 14.8205 mL 29.6410 mL 74.1026 mL
5 mM 0.5928 mL 2.9641 mL 5.9282 mL 14.8205 mL
10 mM 0.2964 mL 1.4821 mL 2.9641 mL 7.4103 mL
15 mM 0.1976 mL 0.9880 mL 1.9761 mL 4.9402 mL
20 mM 0.1482 mL 0.7410 mL 1.4821 mL 3.7051 mL
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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.

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Product Name:
MT-228
Cat. No.:
HY-175199
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