切换导航

MYK-461

现货
Catalog No.
A8720
抑制三磷酸腺苷酶的活性
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,100.00
现货
5mg
¥ 3,500.00
现货
25mg
¥ 12,000.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

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:

A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science, 2016. Vol 351,6273.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt273.33
Cas No.1642288-47-8
FormulaC15H19N3O2
SynonymsMavacamten,SAR439152
Solubility≥13.65mg/mL in DMSO
Chemical Name(S)-3-isopropyl-6-((1-phenylethyl)amino)pyrimidine-2,4(1H,3H)-dione
SDFDownload SDF
Canonical SMILESC[C@H](NC(NC(N1C(C)C)=O)=CC1=O)C2=CC=CC=C2
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

成年大鼠心室心肌细胞

溶解方法

该化合物在DMSO中的溶解度大于13.7 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

IC50: 0.18 mM

应用

MYK-461抑制肌球蛋白ATP酶和心肌细胞的收缩。用MYK-461处理小鼠心脏肌原纤维剂量依赖性地降低ATPase活性。

动物实验 [1]:

动物模型

表达心脏肌球蛋白重链错义突变R403Q、R719W或R453C的HCM小鼠和野生型(WT)小鼠。

给药剂量

每天2.5 mg/kg,通过饮用水给药

应用

MYK-461减少HCM小鼠模型中心肌梗死和纤维化的发展。在成年大鼠心室心肌细胞中,MYK-461剂量依赖性地减少分数缩短而不改变钙瞬变。用MYK-461处理的HCM小鼠具有与WT小鼠相当的左心室壁厚度(LVWT)。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

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.

质量控制