Repositioning Candidate Details
| Candidate ID: | R1082 |
| Source ID: | DB06693 |
| Source Type: | experimental |
| Compound Type: | small molecule |
| Compound Name: | Mevastatin |
| Synonyms: | Compactin; Mevastatin |
| Molecular Formula: | C23H34O5 |
| SMILES: | [H][C@]12[C@H](CCC=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC |
| Structure: |
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| DrugBank Description: | Mevastatin or compactin is a cholesterol-lowering agent isolated from <i>Penicillium citinium</i>. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated by <i>in vivo</i> hydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today. |
| CAS Number: | 73573-88-3 |
| Molecular Weight: | 390.52 |
| DrugBank Indication: | Not used therapeutically due to its many side effects. |
| DrugBank Pharmacology: | The primary cause of cardiovascular disease is atherosclerotic plaque formation. Mevastatin lowers hepatic production of cholesterol to reduce the risk of cardiovascular disease. Mevastatin competitively inhibits HMG-CoA reductase. This inhibition prevents the rate limiting step in cholesterol synthesis. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. |
| DrugBank MoA: | Mevastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Mevastatin is a prodrug that is activated <i>in vivo</i> via hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with 10,000 times greater affinity than its natural substrate. The bicyclic portion of mevastatin binds to the coenzyme A portion of the active site. |
| Targets: | 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor |
| Inclusion Criteria: | Target associated |
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