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  3. MT-110

MT-110 (BPN-0027490) is a non-muscle myosin NMIIB-selective inhibitor with high brain penetration and favorable safety profile. MT-110 specifically disrupts NMIIB-dependent actin dynamics in dendritic spines, while it exerts no significant adverse effects on cardiac myosin II and cardiac functions (such as cardiac output and heart rate) at tested concentrations. A single administration of MT-110 produces long-lasting (sustained for several weeks) blockade of methamphetamine motivation associated with environmental cues. MT-110 exhibits extremely high specificity, with no interference with cocaine motivation, hippocampus-dependent memory, fear memory, or locomotor and anxiety-like behaviors. MT-110 serves as a valuable tool compound for investigating the mechanisms of methamphetamine use disorder.

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MT-110

MT-110 Chemical Structure

CAS No. : 2404652-82-8

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Powder + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Description

MT-110 (BPN-0027490) is a non-muscle myosin NMIIB-selective inhibitor with high brain penetration and favorable safety profile. MT-110 specifically disrupts NMIIB-dependent actin dynamics in dendritic spines, while it exerts no significant adverse effects on cardiac myosin II and cardiac functions (such as cardiac output and heart rate) at tested concentrations. A single administration of MT-110 produces long-lasting (sustained for several weeks) blockade of methamphetamine motivation associated with environmental cues. MT-110 exhibits extremely high specificity, with no interference with cocaine motivation, hippocampus-dependent memory, fear memory, or locomotor and anxiety-like behaviors. MT-110 serves as a valuable tool compound for investigating the mechanisms of methamphetamine use disorder[1].

In Vitro

MT-110 (0-50 μM) potently inhibits non-muscle myosin IIB, non-muscle myosin IIA, smooth muscle myosin II, and skeletal muscle myosin II, and shows no inhibition of cardiac muscle myosin II at concentrations up to 50 μM[1].
MT-110 (0-11 μM; 24 h) potently inhibits NMIIB-dependent cytokinesis in COS-7 cells with an EC50 of 0.68 μM and does not induce cytotoxicity at concentrations up to 11 μM[1].

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

Parmacokinetics
Species Dose Route Tmax T1/2
Mice[1] 2 mg/kg i.v. 0.08 h 3.1 h
In Vivo

MT-110 (0.5-2.5 mg/kg; i.p.; single dose) persistently disrupts methamphetamine-associated conditioned place preference in male C57BL/6 mice for at least 24 hours[1].
MT-110 (1-2 mg/kg; i.v.; single dose) disrupts methamphetamine-seeking behavior in male Sprague-Dawley rats, with the 2 mg/kg dose producing a persistent effect for at least 14 days[1].
MT-110 (7.5 mg/kg; i.p.; single dose) does not disrupt cocaine-associated conditioned place preference in male C57BL/6 mice[1].
MT-110 (0.5-5 mg/kg; i.v.; single infusion) produces no acute adverse effects on cardiac output or heart rate in Sprague-Dawley rats[1].
MT-110 (10-20 mg/kg; i.v.; once weekly; 3 doses) produces no significant adverse effects in male and female Sprague-Dawley rats, with a no adverse effect level equal to or higher than 20 mg/kg[1].
MT-110 (0.5-16.5 mg/kg; i.v.; single dose) does not alter locomotor activity or anxiety-like behavior in male C57BL/6 mice tested in an open field[1].
MT-110 (15-30 mg/kg; i.v.; single dose) produces only modest, non-significant changes in respiratory rate and tidal volume, with no effect on minute volume, in Sprague-Dawley rats[1].

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

Animal Model: C57BL/6 mice (adult, male, 25-30 g, methamphetamine-associated conditioned place preference training)[1]
Dosage: 0.5 mg/kg; 1 mg/kg; 2.5 mg/kg
Administration: i.p.; single dose
Result: Eliminated the significant preference for the methamphetamine-paired chamber observed in vehicle-treated mice.
Produced disruption that persisted for at least 24 hours after a single dose, with no significant chamber preference detected in retesting.
Animal Model: Sprague-Dawley mice (adult, male, methamphetamine self-administration training followed by 4 days of forced abstinence)[1]
Dosage: 1 mg/kg; 2 mg/kg
Administration: i.v.; single dose
Result: Reduced active lever pressing (a measure of methamphetamine seeking) during the first test at 1 mg/kg and 2 mg/kg doses.
Produced a persistent reduction in active lever pressing that remained significant 14 days after the single 2 mg/kg dose.
Animal Model: C57BL/6 mice (adult, male, 25-30 g, cocaine-associated conditioned place preference training)[1]
Dosage: 7.5 mg/kg
Administration: i.p.; single dose
Result: Did not alter the significant preference for the cocaine-paired chamber observed in vehicle-treated mice.
Showed no difference in chamber preference detected between vehicle and MT-110-treated groups.
Animal Model: Sprague-Dawley rats (adult, male and female, healthy)[1]
Dosage: 0.5 mg/kg; 5 mg/kg
Administration: i.v.; single infusion
Result: Produced no significant changes in cardiac output compared to baseline or vehicle controls at both tested doses.
Maintained normal heart rate at all tested doses.
Animal Model: Sprague-Dawley mice (adult, male and female, healthy)[1]
Dosage: 10 mg/kg; 15 mg/kg; 20 mg/kg
Administration: i.v.; once weekly; 3 doses
Result: Caused no significant MT-110-related adverse effects, including no changes in body weight, complete blood count parameters, clinical chemistry values, urinalysis, or histopathologic tissue evaluation.
Noted only intermittent hypoactivity and exopthalmia, with no other toxicities detected.
Animal Model: C57BL/6 mice (adult, male, 25-30 g, healthy)[1]
Dosage: 0.5, 1, 2.5, 6, 12, or 16.5 mg/kg
Administration: i.v.; single dose
Result: Produced no significant changes in distance traveled, average velocity, or time spent in the center versus the sides/corners of the open field compared to vehicle-treated mice.
Showed no effects on locomotion or anxiety-like behavior.
Animal Model: Sprague-Dawley rats (adult, male and female, healthy)[1]
Dosage: 15 mg/kg; 30 mg/kg
Administration: i.v.; single dose
Result: Produced only modest, non-significant increases in respiratory rate (approximately 20% change) and corresponding decreases in tidal volume at both tested doses.
Caused no significant change in minute volume compared to vehicle controls.
Produced only acute transient motor effects (gait changes and stereotypical chewing).
Caused no significant effects on reflexes, physiological measurements (including body temperature, grip strength, and pupillary reflex), or other behavioral endpoints.
Clinical Trial
Molecular Weight

371.43

Formula

C23H21N3O2

CAS No.
Appearance

Powder

Color

Light yellow to yellow

SMILES

O=C1[C@@]2(O)C(N(C3=CC=C4N=C(C)C=CC4=C3)CC2)=NC5=C1C=C(C)C(C)=C5

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 : 100 mg/mL (269.23 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 2.6923 mL 13.4615 mL 26.9230 mL
5 mM 0.5385 mL 2.6923 mL 5.3846 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.

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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    90% Corn Oil

    Solubility: ≥ 2.5 mg/mL (6.73 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:

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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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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 2.6923 mL 13.4615 mL 26.9230 mL 67.3074 mL
5 mM 0.5385 mL 2.6923 mL 5.3846 mL 13.4615 mL
10 mM 0.2692 mL 1.3461 mL 2.6923 mL 6.7307 mL
15 mM 0.1795 mL 0.8974 mL 1.7949 mL 4.4872 mL
20 mM 0.1346 mL 0.6731 mL 1.3461 mL 3.3654 mL
25 mM 0.1077 mL 0.5385 mL 1.0769 mL 2.6923 mL
30 mM 0.0897 mL 0.4487 mL 0.8974 mL 2.2436 mL
40 mM 0.0673 mL 0.3365 mL 0.6731 mL 1.6827 mL
50 mM 0.0538 mL 0.2692 mL 0.5385 mL 1.3461 mL
60 mM 0.0449 mL 0.2244 mL 0.4487 mL 1.1218 mL
80 mM 0.0337 mL 0.1683 mL 0.3365 mL 0.8413 mL
100 mM 0.0269 mL 0.1346 mL 0.2692 mL 0.6731 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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MT-110
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