Omecamtiv-mecarbil-CK-1827452-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOmecamtiv mecarbilCat. No.: HY-14233CAS No.: 873697-71-3Synonyms: CK-1827452分式: CHFNO分量: 401.43作靶点: Myosin作通路: Cytoskeleton储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (124.55 m

2、M; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4911 mL 12.4555 mL 24.9109 mL5 mM 0.4982 mL 2.4911 mL 4.9822 mL10 mM 0.2491 mL 1.2455 mL 2.4911 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液

3、可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.23 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.23 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of Small Molec

4、ules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.23 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Omecamtiv mecarbil肌肌球蛋激活剂。体外研究 Omecamtiv mecarbil (10 M) reduces the maximal ATPase (kcat) 4.5-fold and dramatically reduces the actinconcentration at which ATPase is half-maximal (KATPase) 30-fold. The Ome

5、camtiv mecarbil-inducedinhibition of the actin-activated ATPase is evaluated in a concentration-dependent manner to determine theEC50 (0.52 0.10 M). Omecamtiv mecarbil does not change the overall actin affinity. Omecamtiv mecarbiltraps a population of myosin heads in a weak actin affinity state with

6、 slow product release. Omecamtivmecarbil can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay 3.体内研究 Omecamtiv mecarbil (100-1000 ng/mL) demonstrates concentration-dependent increases in FS inSpragueDawley rats model. Omecamtiv mecarbil demonstrates good PK paramet

7、ers in both rats(SpragueDawley) 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 1. Omecamtiv mecarbil does not affect thephosphorylation status of myofilament proteins in both WT and KO hearts as shown by

8、the absence ofsignificant differences between pre and post Omecamtiv mecarbil samples within WT and KO groups, oraffect the force generation at maximal Ca2+ activation (pCa 4.5) in any of the groups. Omecamtiv mecarbilincreases the responsiveness of the cardiac myofilaments to Ca2+ at submaximal Ca2

9、+-activations 2.REFERENCES1. 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 skin

10、ned myocardium lackingcardiac 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 -Cardiac Myosin Resulting in Increased CalciumSensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778.McePdfHeightCaution: Product has not been fully val