Substance
ID:73988
Names and Identifiers
Synonyms
CK-1827452Omecamtiv mecarbil
IUPAC Traditional name
methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate
IUPAC name
methyl 4-[(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate
Registration numbers
CAS Number
Properties
Pharmacology Properties
Target
calcium channel
Safety Information
Storage Condition
-20°C
Product Information
Salt Data
Free Base
Molecule Details
Research Area
Description
Cancer
Biological Activity
Description
Omecamtiv mecarbil (CK-1827452) is a specific cardiac myosin activator and a clinical drug for left ventricular systolic heart failure.
Targets
IC50
In Vitro
In vitro, Omecamtiv mecarbil selectively activates cardiac myosin by increasing the myosin ATPase rate. [1] In isolated cardiac myocytes, Omecamtiv mecarbil results in increase of myocyte contractility and overcomes of the myosin inhibitor BDM without increasing the calcium transient or inhibiting the PDE pathway. [1]
In Vivo
Omecamtiv mecarbil significantly increases fractional shortening starting at 0.4 mM plasma concentrations in SD rats, sham animals and in rats with heart failure. [1] In conscious dogs with myocardial infarction (MI-sHF), Omecamtiv mecarbil leads to a significant increase in wall thickening (25%), stroke volume (44%), cardiac output (22%) and left ventricular (LV) systolic ejection time (26%). In addition, Omecamtiv mecarbil also results in the decreases of some hemodynamic parameters including heart rate, mean left atrial pressure, and LV end-diastolic pressure. In conscious dogs with left ventricular hypertrophy (LVH-sHF), Omecamtiv mecarbil leads to similar and not statistically different effects on hemodynamic parameters. [2]
Clinical Trials
Omecamtiv mecarbil is currently in Phase II clinical trials in patients with Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure.
Features
Protocol
Kinase Assay [1]
Biochemical assays
Cardiac S1 myosin and thin filament proteins (actin, troponin complex, and tropomyosin) are prepared from bovine heart or rabbit skeletal muscle. Smooth muscle myosin is prepared from chicken gizzard. ATPase assays are performed in a kinetic fashion using NADH coupled enzyme system at pCa2+ = 6.75. Rates are normalized to a DMSO control.
Cell Assay []
Animal Study [1]
Animal Models
Sprague Dawley rats.
Formulation
Omecamtiv mecarbil is dissolved in DMSO and then diluted in water.
Doses
≤1.2 mg/kg/hour
Administration
Administered via i.v.
Molecular Spectra
No Data Available
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References
• Shen YT, et al. Circ Heart Fail. 2010, 3(4), 522-577.
• Anderson RL, et al. Mol Bio Cell, 2005, 16 (Abstract #1728).