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作靶點(diǎn): Myosin作通路: Cytoskeleton儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (124.55 m

2、M; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液

3、可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.23 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.23 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molec

4、ules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (6.23 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Omecamtiv mecarbil肌肌球蛋激活劑。體外研究 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.體內(nèi)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