CK-1827452 is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. Omecamtiv Mecarbil 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.
Chemical Formula: C20H24FN5O3
Exact Mass: 401.1863
Molecular Weight: 401.43
Elemental Analysis: C, 59.84; H, 6.03; F, 4.73; N, 17.45; O, 11.96
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)
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
Omecamtiv mecarbil (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 Omecamtiv mecarbil-induced inhibition of the actin-activated ATPase is evaluated in a concentration-dependent manner to determine the EC50 (0.52 ± 0.10 μM). Omecamtiv mecarbil does not change the overall actin affinity. Omecamtiv mecarbil traps a population of myosin heads in a weak actin affinity state with slow product release. Omecamtiv mecarbil can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay.
Omecamtiv mecarbil (100-1000 ng/mL) demonstrates concentration-dependent increases in FS in Sprague−Dawley rats model. Omecamtiv mecarbil 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. Omecamtiv mecarbil 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 Omecamtiv mecarbil samples within WT and KO groups, or affect the force generation at maximal Ca2+ activation (pCa 4.5) in any of the groups. Omecamtiv mecarbil increases the responsiveness of the cardiac myofilaments to Ca2+ at submaximal Ca2+-activations.
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