Description
Everolimus-d
4 is intended for use as an internal standard for the quantification of everolimus by GC- or LC-MS. Everolimus is a hydroxyethyl ether form of rapamycin that inhibits mTOR signaling through both mTORC1 and mTORC2 when added to cells at 20 nM. It is orally available and shows improved pharmacokinetics and pharmacodynamics over rapamycin. Through its inhibition of mTOR, everolimus inhibits cell proliferation, metabolism, and angiogenesis in certain types of cancer. It also acts as an immunosuppressive agent in the context of organ transplantation.
Uses
Macrolide immunosuppressant; derivative of Rapamycin. Inhibits cytokine-mediated lymphocyte proliferation.
General Description
A stable-labeled internal standard for the immunosuppressant Everolimus, marketed as Zortress
and Certican for use in organ transplantation and Afinitor
for treatment of kidney and pancreatic cancers. Clinical laboratories quantitate everolimus levels in patient whole blood samples using LC-MS/MS. While many everolimus LC-MS/MS methods use 32-desmethoxyrapamycin or ascomycin as an internal standard, higher levels of variability / lower levels of reproducibility may occur in the analysis along with the potential for interferences. Use of a stable-labeled analog of everolimus is the best choice to minimize variability or mitigate any potential interference in LC-MS/MS analysis.
References
[1] ZHIHONG ZENG. Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.[J]. Blood, 2007, 109 8: 3509-3512. DOI:
10.1182/blood-2006-06-030833[2] DAVID LEBWOHL. Development of everolimus, a novel oral mTOR inhibitor, across a spectrum of diseases[J]. Annals of the New York Academy of Sciences, 2013, 1291 1: 14-32. DOI:
10.1111/nyas.12122[3] MAYU YUNOKAWA. Efficacy of everolimus, a novel mTOR inhibitor, against basal-like triple-negative breast cancer cells[J]. Cancer Science, 2012, 103 9: 1665-1671. DOI:
10.1111/j.1349-7006.2012.02359.x[4] CHERYLE GURK-TURNER Matthew C Wana Manitpisitkul. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor.[J]. Transplantation, 2012, 94 7: 659-668. DOI:
10.1097/tp.0b013e31825b411c
