Name | MYK-461 |
Synonyms | MYK461 MYK-461 SAR-439152 Mavacamten (MYK-461 2,4(1H,3H)-Pyrimidinedione, 3-(1-methylethyl)-6-[[(1S)-1-phenylethyl]amino]- |
CAS | 1642288-47-8 |
Molecular Formula | C15H19N3O2 |
Molar Mass | 273.33 |
Density | 1.19±0.1 g/cm3(Predicted) |
pKa | 8.83±0.40(Predicted) |
Storage Condition | -20℃ |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 0 ml | 0 ml | 0 ml |
5 mM | 0 ml | 0 ml | 0 ml |
10 mM | 0 ml | 0 ml | 0 ml |
5 mM | 0 ml | 0 ml | 0 ml |
biological activity
Mavacamten (MYK-461, SAR439152) is a small molecule regulator of myocardial myosin (cardiac myosin), which regulates hyperganglionic contraction in hypertrophic cardiomyopathy.
in vitro studies
MYK-461 reduces the activity of steady-state ATPase by inhibiting the phosphate release rate of β-cardiac myosin-S1. The MYK-461 regulates multiple steps in the myosin chemomechanical cycle: In addition to reducing the rate-limiting step in the cycle (phosphoric acid release),MYK-461 also reducing the number of myosin-S1 heads (myosin-S1 heads can interact with actin filaments when the weak binding state transitions to the strong binding state). MYK-461 also reduces the rate of myosin binding to ADP-actin and the rate of ADP release from myosin-S1.
In vivo studies
In a mouse model transplanted with myosin heavy chains containing human heterozygous mutations, early and long-term MYK-461 administration (MYK-461) can inhibit the development of ventricular hypertrophy, myocardial cell disorder and myocardial fibrosis, and reduce the expression of hypertrophy and fibrosis-related genes.