MYK-461
(Synonyms: 玛伐凯泰,MYK461; SAR439152) 目录号 : GC15858
A cardiac myosin ATPase inhibitor
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 | |
| 别名 | 玛伐凯泰,MYK461; SAR439152 | ||
| 化学名 | (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 | ||
| 分子式 | C15H19N3O2 | 分子量 | 273.33 |
| 溶解度 | ≥ 13.65mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet