Mavacamten

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Mavacamten (SAR-439152, MYK-461) 是一种小分子，通过降低心肌肌球蛋白重链的 ATP 酶活性来降低收缩力。

Mavacamten (SAR-439152, MYK-461) is a small molecule that reduces contractility by decreasing the ATPase activity of the cardiac myosin heavy chain; inhibits α and β isoforms of cardiac myosin with similar activity (IC50=0.3 uM); suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain.Other Indication Phase 2 Clinical(In Vitro):Mavacamten is found to have an IC50 value of 490 nM in the bovine system, 711 nM in the human system, and 2140 nM in the rabbit system, indicating selectivity of >4-fold for cardiac myosin. (In Vivo):Treatment with Mavacamten reduces FS from 52±3% to 38±7%. Treatment with Mavacamten reduces FS from 81±7% to 60±13%, corresponding to a relative reduction of 25%. Across all measurements there is a linear correlation between FS and Mavacamten plasma concentrations with each 100 ng/mL increase in Mavacamten concentration lowering FS by 4.9%. Treatment with Mavacamten eliminates SAM in 5/5 subjects, whereas SAM persists in 3/3 subjects treated with vehicle alone. Pressure gradients across the LVOT drop to 11.1±5.0 mmHg with Mavacamten treatment; whereas vehicle treated cats maintain stable LVOT pressure gradients. Mavacamten reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Chronic administration of Mavacamten suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain.

Mavacamten is found to have an IC50 value of 490 nM in the bovine system, 711 nM in the human system, and 2140 nM in the rabbit system, indicating selectivity of >4-fold for cardiac myosin.

Treatment with Mavacamten reduces FS from 52±3% to 38±7%. Treatment with Mavacamten reduces FS from 81±7% to 60±13%, corresponding to a relative reduction of 25%. Across all measurements there is a linear correlation between FS and Mavacamten plasma concentrations with each 100 ng/mL increase in Mavacamten concentration lowering FS by 4.9%. Mavacamten reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Chronic administration of Mavacamten suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain.

SAR-439152 | MYK-461

Cytoskeleton/Cell Adhesion Molecules

Myosin

Myosin

Other Indications

Other Disease

1642288-47-8

273.336

C15H19N3O2

>98% (HPLC)

10 mM in DMSO

O=C1N(C(C)C)C(C=C(N[C@H](C2=CC=CC=C2)C)N1)=O

(S)-3-isopropyl-6-((1-phenylethyl)amino)pyrimidine-2,4(1H,3H)-dione

(-20℃)

With Ice Pack

≥ 2 years