A cardiac-specific myosin activator
Omecamtiv mecarbil (CK-1827452) is the first potent cardiac myosin activator that can specifically activate the cardiac myosin S1 domain but not other muscle myosins. In clinical trials, omecamtiv mecarbil has been considered as a promising therapeutic approach to treat systolic heart failure1.
Omecamtiv mecarbil accelerates the actin-dependent Pi release from cardiac myosin S1 domain, thus increases the rate of transition from weakly actin-bound state to strongly actin-bound state (EC50= 2.3 μM)1.
At the concentration of 200nM, omecamtiv mecarbil was reported to remarkably increase the contractility of adult rat cardiac myocytes without influencing calcium transient. In vivo, Omecamtiv mecarbil has been shown to improve cardiac function without changing myocardial oxygen consumption in both beagle dogs and Sprague-Dawley rats under isoflurane anesthesia1.
参考文献:
1.?Malik FI1, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R, Baliga R, Cox DR, Garard M,Godinez G, Kawas R, Kraynack E, Lenzi D, Lu PP, Muci A, Niu C, Qian X, Pierce DW, Pokrovskii M, Suehiro I, Sylvester S, Tochimoto T, Valdez C, Wang W,Katori T, Kass DA, Shen YT, Vatner SF, Morgans DJ. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43.
| Cell experiment [1]: | |
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Cell lines |
Cardiac myocytes |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
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Reaction Conditions |
200 nM |
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Applications |
Omecamtiv Mecarbil extended the duration of contraction without affecting the rates of contraction or relaxation. In addition, Omecamtiv Mecarbil also increased myocyte contraction in the presence of a β-adrenergic blocker, Carvedilol. |
| Animal experiment [1]: | |
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Animal models |
Conscious and heart failure dogs |
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Dosage form |
A bolus at 0.5 mg/kg, followed by infusion at 0.5 mg/kg per hr |
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Applications |
In a conscious canine model, Omecamtiv Mecarbil improved left ventricular systolic function. In heart failure dogs, Omecamtiv Mecarbil significantly increased stroke volume and cardiac output. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Malik FI1, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R, Baliga R, Cox DR, Garard M,Godinez G, Kawas R, Kraynack E, Lenzi D, Lu PP, Muci A, Niu C, Qian X, Pierce DW, Pokrovskii M, Suehiro I, Sylvester S, Tochimoto T, Valdez C, Wang W,Katori T, Kass DA, Shen YT, Vatner SF, Morgans DJ. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011 Mar 18;331(6023):1439-43. |
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