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.

Physicochemical Properties

Molecular Formula	C20H24FN5O3
Molecular Weight	401.43
Exact Mass	401.186
CAS #	873697-71-3
Related CAS #	Omecamtiv mecarbil-d8
PubChem CID	11689883
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	456.8±45.0 °C at 760 mmHg
Melting Point	180℃
Flash Point	230.1±28.7 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.639
LogP	1.36
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	558
Defined Atom Stereocenter Count	0
InChi Key	RFUBTTPMWSKEIW-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H24FN5O3/c1-14-6-7-16(12-22-14)23-19(27)24-17-5-3-4-15(18(17)21)13-25-8-10-26(11-9-25)20(28)29-2/h3-7,12H,8-11,13H2,1-2H3,(H2,23,24,27)
Chemical Name	methyl 4-[[2-fluoro-3-[(6-methylpyridin-3-yl)carbamoylamino]phenyl]methyl]piperazine-1-carboxylate
Synonyms	CK1827452; CK 1827452; CK1827452; Omecamtiv mecarbil.
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
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].
Animal Protocol	Dissolved in DMSO and then diluted in water; ≤1.2 mg/kg/hour; i.v. injection. Sprague Dawley rats.
References	[1]. 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]. 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]. 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.
Additional Infomation	Omecamtiv mecarbil is a member of ureas. Omecamtiv Mecarbil has been used in trials studying the treatment and basic science of Heart Failure, Echocardiogram, Pharmacokinetics, Chronic Heart Failure, and History of Chronic Heart Failure, among others. Drug Indication Treatment of heart failure

Solubility Data

Solubility (In Vitro)

DMSO: 80 mg/mL (199.3 mM) Water:<1 mg/mL Ethanol: 6 mg/mL (14.9 mM)

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. 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. 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 corn oil and mix evenly. Solubility in Formulation 4: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

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.