| Systematic (IUPAC) name | |
|---|---|
| dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone | |
| Clinical data | |
| Licence data | US FDA:link |
| Pregnancy cat. | D(US) |
| Legal status | ℞ Prescription only |
| Routes | Oral |
| Pharmacokinetic data | |
| Half-life | ~30 hours[1] |
| Identifiers | |
| CAS number | 159351-69-6 |
| ATC code | L01XE10 L04AA18 |
| PubChem | CID 6442177 |
| DrugBank | DB01590 |
| ChemSpider | 21106307 |
| UNII | 9HW64Q8G6G |
| KEGG | D02714 |
| ChEMBL | CHEMBL1201755 |
| Synonyms | 42-O-(2-hydroxyethyl)rapamycin |
| Chemical data | |
| Formula | C53H83NO14 |
| Mol. mass | 958.224 g/mol |
| SMILES | eMolecules & PubChem |
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Everolimus (RAD-001) is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an mTOR (mammalian target of rapamycin) inhibitor.
It is currently used as an immunosuppressant to prevent rejection of organ transplants and treatment of renal cell cancer. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.
It is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and Afinitor in oncology.
Contents |
Everolimus is approved for various conditions:
As of October 2010[update], Phase III trials are under way in breast cancer, gastric cancer, hepatocellular carcinoma and lymphoma.[6]
Interim phase III trial results in 2011 show that adding Afinitor (everolimus) to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.[7]
In a similar fashion to other mTOR inhibitors its effect is solely on the mTORC1 protein and not on the mTORC2 protein. This can lead to a hyper-activation of the kinase AKT via inhibition on the mTORC1 negative feedback loop while not inhibiting the mTORC2 positive feedback to AKT. This AKT elevation can lead to longer survival in some cell types.
Everolimus may have a role in heart transplantation as it has been shown to reduce chronic allograft vasculopathy in such transplants. It also may have a similar role to sirolimus in kidney and other transplants.[8]
Because hypercholesterolemia and hypertriglyceridemia have been reported, monitoring of blood lipid level is recommended.
Everolimus is used in drug-eluting coronary stents as an immunosuppressant to prevent restenosis. Abbott Vascular produces an everolimus-eluting stent called the Xience V. It utilizes the Multi-Link Vision cobalt chromium stent platform and Novartis' everolimus. The product is also currently an investigational device in the United States and Japan. It is also available under a private-label version called the PROMUS Everolimus-Eluting Coronary Stent System and it is currently available in most major European and Asia-Pacific markets.
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