MYK-461 (Synonyms: MYK-461, SAR439152) |
| Catalog No.GC15858 |
MYK-461 (MYK461) is an orally active modulator of cardiac myosin, with IC50s of 490, 711 nM for bovine cardiac and human cardiac, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1642288-47-8
Sample solution is provided at 25 µL, 10mM.
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MYK-461 is a small molecular chemical that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain.
MYK-461 reduced ATPase activity in a dose-dependent manner with IC50 value of 0.3 mM after treatment of mouse cardiac myofibrils. MYK-461 (>10 mM) decreased the maximal ATPase rate by ~90%. MYK-461 is active against both the A and B isoforms of cardiac myosin.
Treatment with MYK-461 decreased the rate of phosphate release in a dose-dependent manner without slowing adenosine diphosphate (ADP) release. MYK-461 decreases the myosin duty ratio and thus reduces the ensemble power, force and contractility produced by the sarcomere. Exposure to MYK-461 reduced maximal tension in a dose-dependent manner (~70% reduction at 1.0 mM) without altering the pCa50 or the tension at lower calcium concentrations.
MYK-461 showed a dose-dependent reduction in fractional shortening (IC50=0.18 mM) without changing the calcium transient after treated with adult rat ventricular cardiomyocytes. MYK-461 plasma exposures decreased fractional shortening in WT and mutant mice. Although MYK-461 inhibits the ATPase activity of skeletal myosin with a lower affinity (IC50 of 4.7 mM with rabbit skeletal myosin), treated rodents had no reduction in grip strength or voluntary exercise capacity. MYK-461 reduced cardiac contractility in a dose-dependent manner in normal and mutant mice without overt impairment of skeletal muscle function. MYK-461 was administered after the development of substantial hypertrophy, it did not significantly reduce the occurrence of fibrosis. Prehypertrophic R403Q mice treated with MYK-461 had 30% more aligned cardiomyocytes (59 ± 10%; P = 0.02).
Reference:
[1].A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science, 2016. Vol 351,6273.
| Cell experiment [1]: | |
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Cell lines |
Adult rat ventricular cardiomyocytes |
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Preparation method |
The solubility of this compound in DMSO is >13.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
IC50: 0.18 mM |
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Applications |
MYK-461 inhibited myosin ATPase and contractility of cardiomyocytes. Treatment of mouse cardiac myofibrils with MYK-461 dose-dependently reduced ATPase activity. |
| Animal experiment [1]: | |
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Animal models |
Wild-type (WT) and HCM mice expressing a–cardiac myosin heavy chain missense mutations R403Q, R719W, or R453C. |
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Dosage form |
2.5 mg/kg per day via drinking water. |
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Application |
MYK-461 reduced the development of myocardial disarray and fibrosis in mouse models of HCM. In adult rat ventricular cardiomyocytes, MYK-461 dose-dependently reduced the fractional shortening without changing the calcium transient. HCM mice treated with MYK-461 had left ventricular wall thickness (LVWT) comparable to that of WT mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Green E M, Wakimoto H, Anderson R L, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice[J]. Science, 2016, 351(6273): 617-621. | |
| Cas No. | 1642288-47-8 | SDF | |
| Synonyms | MYK-461, SAR439152 | ||
| Chemical Name | (S)-3-isopropyl-6-((1-phenylethyl)amino)pyrimidine-2,4(1H,3H)-dione | ||
| Canonical SMILES | C[C@H](NC(NC(N1C(C)C)=O)=CC1=O)C2=CC=CC=C2 | ||
| Formula | C15H19N3O2 | M.Wt | 273.33 |
| Solubility | ≥ 13.65mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.6586 mL | 18.2929 mL | 36.5858 mL |
| 5 mM | 0.7317 mL | 3.6586 mL | 7.3172 mL |
| 10 mM | 0.3659 mL | 1.8293 mL | 3.6586 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 1 reference(s) in Google Scholar.)
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