CK-1827452 is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. CK-1827452 specifically targets and activates myocardial ATPase and improves energy utilization. CK-1827452 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.
CAS Number: 873697-71-3
Molecular Weight: 401.43
Chemical Name: methyl4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Soluble in DMSO, not in water
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
CK-1827452 (10 μM) reduces the maximal ATPase (kcat) 4.5-fold and dramatically reduces the actin concentration at which ATPase is half-maximal (KATPase) 30-fold. The CK-1827452-induced inhibition of the actin-activated ATPase is evaluated in a concentration-dependent manner to determine the EC50 (0.52 ± 0.10 μM). CK-1827452 does not change the overall actin affinity. CK-1827452 traps a population of myosin heads in a weak actin affinity state with slow product release. CK-1827452 can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay.
CK-1827452 (100-1000 ng/mL) demonstrates concentration-dependent increases in FS in Sprague−Dawley rats model. CK-1827452 demonstrates good PK parameters in both rats (Sprague−Dawley) and dogs (Beagle) 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. CK-1827452 does not affect the phosphorylation status of myofilament proteins in both WT and KO hearts as shown by the absence of significant differences between pre and post CK-1827452 samples within WT and KO groups, or affect the force generation at maximal Ca2+ activation (pCa 4.5) in any of the groups. CK-1827452 increases the responsiveness of the cardiac myofilaments to Ca2+ at submaximal Ca2+-activations.
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