Repositioning Candidate Details
| Candidate ID: | R0393 |
| Source ID: | DB01074 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Perhexiline |
| Synonyms: | Perhexilene; Perhexiline |
| Molecular Formula: | C19H35N |
| SMILES: | C(C(C1CCCCC1)C1CCCCC1)C1CCCCN1 |
| Structure: |
|
| DrugBank Description: | Perhexiline is a coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. |
| CAS Number: | 6621-47-2 |
| Molecular Weight: | 277.4879 |
| DrugBank Indication: | For the management of severe angina pectoris. |
| DrugBank Pharmacology: | Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures. |
| DrugBank MoA: | Perhexiline binds to the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1 and CPT-2. It acts by shifting myocardial substrate utilisation from long chain fatty acids to carbohydrates through inhibition of CPT-1 and, to a lesser extent, CPT-2, resulting in increased glucose and lactate utilization. This results in increased ATP production for the same O2 consumption as before and consequently increases myocardial efficiency. |
| Targets: | Carnitine O-palmitoyltransferase 1, liver isoform inhibitor; Carnitine O-palmitoyltransferase 2, mitochondrial inhibitor; Potassium voltage-gated channel subfamily H member 2 |
| Inclusion Criteria: | Indication associated |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |