There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
MYK-461 is a myosin inhibitor potentially for the treatment of hypertrophic cardiomyopathy, and can reduce contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain.
Mavacamten 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Adult rat ventricular cardiomyocytes
0.18 µM (IC50)
MYK-461 reduced fractional shortening in a dose-dependent manner without altering calcium transients
Science. 2016 Feb 5;351(6273):617-21.
Mouse cardiac myofibrils
0.3 µM (IC50)
MYK-461 reduced ATPase activity in a dose-dependent manner, with maximal doses (>10 µM) reducing the ATPase rate by ~90%
Science. 2016 Feb 5;351(6273):617-21.
Rabbit psoas myofibrils
0.1-50 µM
Mavacamten decreased the kinetics of force development in fast skeletal myofibrils, while it had no effect in human ventricular myofibrils.
J Gen Physiol. 2021 Jul 5;153(7):e202012789.
Human ventricular myofibrils
0.1-50 µM
Mavacamten had a fast, fully reversible, and dose-dependent negative effect on maximal Ca2+-activated isometric force at 15°C, which can be explained by a sudden decrease in the number of heads functionally available for interaction with actin.
J Gen Physiol. 2021 Jul 5;153(7):e202012789.
Mavacamten 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
HCM Mice models expressing α-cardiac myosin heavy chain missense mutations (R403Q, R719W, or R453C)
Oral administration in drinking water
2.5 mg/kg
Daily administration for 20 to 26 weeks (preventive treatment) or 4 weeks (reversal treatment)
MYK-461 reduced cardiac contractility in a dose-dependent manner, prevented or ameliorated left ventricular hypertrophy (LVH), reduced myocardial fibrosis and cardiomyocyte disarray, and improved gene expression profiles
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