Everolimus

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Everolimus
Systematic (IUPAC) name
?
Identifiers
CAS number	159351-69-6
ATC code	L04AA18
PubChem	6442177
Chemical data
Formula	C53H83NO14
Mol. mass	958.224 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

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Everolimus (RAD-001) (marketed as Certican by Novartis) is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. Much research has also been conducted on Everolimus and other mTOR inhibitors for use in a number of cancers.

Although it does not have FDA approval in the USA, it is approved for use in Europe and Australia, and Phase III trials are being conducted in the US.

Role in heart transplantation

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.^[1]

Contraindications

The contra-indication in the use of everolimus is a certain rise in cholesterol levels and therefore an increased cardio-vascular risk.

Mechanism

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 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.

Use in stents

Everolimus is used in drug-eluting coronary stents as an immunosuppressant to prevent rejection. A company called Abbott Vascular produces an everolimus-eluting stent called the Xience V. It is approved for sale and available in Europe. 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.

References

1. ↑ Eisen HJ, Tuzcu EM, Dorent R, et al: Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients. New England Journal of Medicine 2003; 349:847-858

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Chemical modification of rapamycin: the discovery of SDZ RAD. PMID: 9723437