Repositioning Candidate Details
| Candidate ID: | R0333 |
| Source ID: | DB00922 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Levosimendan |
| Synonyms: | Levosimendan |
| Molecular Formula: | C14H12N6O |
| SMILES: | C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1 |
| Structure: |
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| DrugBank Description: | Levosimendan increases calcium sensitivity to myocytes by binding to troponin C in a calcium dependent manner. This increases contractility without raising calcium levels. It also relaxes vascular smooth muscle by opening adenosine triphosphate sensitive potassium channels. Levosimendan is used to manage acutely decompensated congestive heart failure. |
| CAS Number: | 141505-33-1 |
| Molecular Weight: | 280.2847 |
| DrugBank Indication: | For short term treatment of acutely decompensated severe chronic heart failure (CHF). Also being investigated for use/treatment in heart disease. |
| DrugBank Pharmacology: | Levosimendan is a new Ca<sup>2+</sup>-sensitizing inotropic agent. Ca<sup>2+</sup> sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca<sup>2+</sup> overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada. |
| DrugBank MoA: | Levosimendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, thereby (1) changing actin-myosin cross-bridge kinetics apparently without increasing the cycling rate of the cross-bridges or myocardial ATP consumption, (2) increasing the effects of calcium on cardiac myofilaments during systole and (3) improving contraction at low energy cost (inotropic effect). Calcium concentration and, therefore, sensitization decline during diastole, allowing normal or improved diastolic relaxation. Levosimendan also leads to vasodilation through the opening of ATP-sensitive potassium channels. By these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand. Levosimendan also has a selective phosphodiesterase (PDE)-III inhibitory action that may contribute to the inotropic effect of this compound under certain experimental conditions. It has been reported that levosimendan may act preferentially as a Ca<sup>2+</sup> sensitizer at lower concentrations, whereas at higher concentrations its action as a PDE-III inhibitor becomes more prominent in experimental animals and humans. |
| Targets: | Troponin C, slow skeletal and cardiac muscles potentiator; ATP-sensitive inward rectifier potassium channel 11 inducer; ATP-sensitive inward rectifier potassium channel 8 inducer; cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I08 | 114 | Cardiovascular system disease | A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system | disease of anatomical entity | Details |