Repositioning Candidate Details
| Candidate ID: | R1210 |
| Source ID: | DB09069 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Trimetazidine |
| Synonyms: | 1-[2,3,4-trimethoxybenzyl] piperazine dihydrochloride; Trimetazidine |
| Molecular Formula: | C14H22N2O3 |
| SMILES: | COC1=C(OC)C(OC)=C(CN2CCNCC2)C=C1 |
| Structure: |
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| DrugBank Description: | Trimetazidine is a piperazine derivative indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. Trimetazidine has been studied as a treatment for angina pectoris since the late 1960s. Acidic conditions, caused by anaerobic metabolism and fatty acid oxidation, in response to myocardial ischemia, activate sodium-hydrogen and sodium-calcium antiport systems. The increased intracellular calcium decreases contractility. It is hypothesized that trimetazidine inhibits 3-ketoacyl coenzyme A thiolase, which decreases fatty acid oxidation but not glucose metabolism, preventing the acidic conditions that exacerbate ischemic injury. However, evidence for this mechanism is controversial. Trimetazidine is not FDA approved. However, it has been approved in France since 1978. |
| CAS Number: | 5011-34-7 |
| Molecular Weight: | 266.341 |
| DrugBank Indication: | Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. |
| DrugBank Pharmacology: | Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies. Patients should be counselled regarding the risk of use with reduced renal or hepatic function, worsening of extrapyramidal symptoms or other movement disorders, and risk of falls. |
| DrugBank MoA: | During myocardial ischemia, anaerobic metabolism takes over, increasing levels of lactic acid. The decreased intracellular pH and increased concentration of protons activates sodium-hydrogen and sodium-calcium antiport systems, raising intracellular calcium concentrations, finally leading to decreased contractility. This injury to the myocardium raises concentrations of catecholamines, which activate hormone sensitive lipase, and increasing fatty acid concentrations in plasma. When the myocardium is repurfused, fatty acid oxidation becomes the dominant form of ATP production, maintaining an acidic pH, and further exacerbating the injury. The mechanism of action of trimetazidine is not fully understood. Trimetazidine may inhibit mitochondrial 3-ketoacyl coenzyme A thiolase, decreasing long chain fatty acid β-oxidation but not glycolysis in the myocardium. The decreased long chain fatty acid β-oxidation is compensated for by increased use of glucose, preventing a lowered myocardial pH, and further decreases in contractility. However, another study suggests that 3-ketoacyl coenzyme A thiolase may not be trimetazidine's target, and that this mechanism may be incorrect. |
| Targets: | 3-ketoacyl-CoA thiolase, mitochondrial 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 |