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2mg |
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5mg |
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25mg |
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100mg |
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Purity: ≥98%
Omecamtiv mecarbil (also known as CK-1827452) is a specific/selective cardiac myosin activator and a clinical drug for left ventricular systolic heart failure. Omecamtiv mecarbil is clinically investigated for its role in the treatment of left ventricular systolic heart failure. It specifically targets and activates myocardial ATPase and improves energy utilization. Omecamtiv Mecarbil improves systolic function by increasing the systolic ejection duration/stroke volume, without consuming more ATP energy, oxygen or altering intracellular calcium levels causing an overall improvement in cardiac efficiency.
ln Vitro |
Omecamtiv mecarbil (10 μM) significantly lowers the actin concentration at which ATPase is half-maximal (KATPase) by 30 times and the maximal ATPase (kcat) by 4.5 times. The concentration-dependent evaluation of the actin-activated ATPase inhibition mediated by omecamtiv mecarbil yields the EC50 value of 0.52 ± 0.10 μM. The total actin affinity is unchanged by omecamtiv mecarbil. Slow product release is achieved with omecamtiv mecarbil, which traps a population of myosin heads in a weak actin affinity condition. In the in vitro motility assay, omecamtiv mecarbil can reduce the actin sliding velocity by more than 100 times[3].
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ln Vivo |
Among Sprague, omecamtiv mecarbil (100-1000 ng/mL) exhibits concentration-dependent increases in FS.Model of Dawley rats. In both rats (Sprague-Dawley) and dogs (Beagle), omecamtiv mecarbil has good PK characteristics, with clearances of 22 and 7.2 mL /min/kg, volumes of 3.5 and 3.6 L/kg, and bioavailabilities (F%) of 100 and 80%, respectively[1]. Omecamtiv mecarbil does not alter the force generation at maximal Ca2+ activation (pCa 4.5) in any of the groups, nor does it alter the phosphorylation status of myofilament proteins in both WT and KO hearts, as demonstrated by the lack of significant differences between pre and post Omecamtiv mecarbil samples within WT and KO groups. The cardiac myofilaments' reactivity to Ca2+ is enhanced by omecamtiv mecarbil at submaximal Ca2+-activations[2].
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Animal Protocol |
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References |
[1]. Morgan BP, et al. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7.
[2]. Mamidi R, et al. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J Mol Cell Cardiol. 2015 Aug;85:262-72. [3]. Swenson AM, et al. Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778. |
Molecular Formula |
C20H24FN5O3
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Molecular Weight |
401.43
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CAS # |
873697-71-3
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Related CAS # |
Omecamtiv mecarbil-d8
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C(N1CCN(CC1)CC2=C(C(NC(NC3=CC=C(N=C3)C)=O)=CC=C2)F)OC
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30 mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4911 mL | 12.4555 mL | 24.9109 mL | |
5 mM | 0.4982 mL | 2.4911 mL | 4.9822 mL | |
10 mM | 0.2491 mL | 1.2455 mL | 2.4911 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04464525 | Withdrawn | Drug: Omecamtiv mecarbil | Chronic Heart Failure With Reduced Ejection Fraction |
Cytokinetics | December 18, 2020 | Phase 3 |
NCT01077167 | Withdrawn | Drug: Omecamtiv mecarbil | Heart Failure | Cytokinetics | July 2010 | Phase 2 |
NCT03759392 | Completed | Drug: Omecamtiv Mecarbil Drug: Placebo |
Heart Failure With Reduced Ejection Fraction |
Cytokinetics | April 9, 2019 | Phase 3 |
NCT00748579 | Terminated | Drug: CK-1827452 | Heart Failure | Cytokinetics | September 2008 | Phase 2 |
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