|Everolimus Chemical Properties|
|storage temp. ||−20°C|
|Everolimus Usage And Synthesis|
|Sirolimus derivatives||Everolimus is sirolimus derivatives. It is also known as 40 - O - (2 - hydroxyethyl) - rapamycin, or 40 - O - (2 - hydroxyethyl) - sirolimus, and it is belong to kinase drugs which interfere with cell communication and prevent tumor cell growth. It is a kind of oral mammals of rapamycin (mTOR) inhibitors, and is mainly used to prevent clinical renal transplantation and rejection after heart transplant surgery. Now it can also be used in the treatment in patients with advanced kidney cancer who has used two kinds of inhibition of vascular endothelial growth factor receptor kinase inhibitors: chougny for sunitinib (Sutent, Pfizer) and sorafenib (Nexavar, bayer) and has less side effects. |
Sunitinib and sorafenib are kinase inhibitor (role in a variety of targeted cells), and everolimus blocks the target of rapamycin (mTOR) specific proteins of mammals, which disturb cancer cell growth, differentiation and metabolism. The mTOR dysregulation in some tumors. Everolimus combined with intracellular protein FKBP - 12 to generate inhibition of complex, thus inhibits mTOR kinase activity, and reduces the mTOR downstream effector S6 ribosomal protein kinase (S6K1) and eukaryotic extension factor 4 e binding protein (4 e - BP) activity at the same time. In addition everolimus inhibits expression of hypoxia-inducible factor (HIF - 1) and reduces the expression of vascular endothelial growth factor (VEGF). Studies have shown that it can decrease the in vivo and in vitro cell proliferation, angiogenesis, and glucose uptake.
1, mTOR is a serine, threonine kinase, P13K/AKT downstream products.
2, sirolimus is also called rapamycin.
|Mammalian target of rapamycin||The activation of rapamycin target molecule (mTOR) will promote the proliferation and survival of cancer cells, at the same time it can also cause blood vessels origin way signaling in endothelial cells. Rapamycin combined with intracellular protein to produce FK506 - binding protein 12 (FKBP12), the resulting protein drug compounds can inhibit mTOR kinase activity. Rapamycin has the effect of immunosuppression, antifungal, antiviral, antitumor activity, blood vessels protection function, but its main application is its immune inhibition, and was approved by the FDA for anti-rejection treatment in organ transplantation in 1999. Many rapamycin derivatives have been synthesized mainly to improve the drug characteristics, these efforts also resulted in the vein for treatment of renal cancer carry rui Selma (temsirolimus) and oral use according to the dimension of therapy (everolimus) discovery and research. Everolimus has been approved for the treatment of rejection after organ transplantation by Europe in 2003, and was subject to market in the name of Certica.|
The above information is edited by the Chemicalbook Duan Yalan.
|Treatment of advanced kidney cancer||Kidney cancer accounts for 2-3% of cancer, early kidney cancer is priority to surgery, the late is given priority to with chemotherapy, and are often poor response to chemotherapy and radiotherapy. In fact, the usage of interleukin 2 alone or combined alpha interferon on immune therapy are limited in clinical due to its toxicity and the generally poor response to treatment. |
Renal cell carcinoma is the most common type of kidney cancer, disease in renal tubular epithelial cells. Usually, this kind of cancer cells in patients can produce resistance to radiotherapy and chemotherapy in standard treatment, such as to make the most of the people through the treatment of kidney remove. If patients with cancerous parts only limit in the kidney, 60-70% of the patients will survive for five years, but if the cancer cells transfer, the life patients survival will be greatly reduced.
On March 30, 2009, Novartis original immunosuppressive drug everolimus(everolimus, Afinitor) used for kidney obtained FDA approval. The results showed that, everolimus can obviously increase progression-free survival of cancer patients. It provides a new treatment option for advanced renal cell cancer patients of no avail to Sunitinib or Sorafenib.
In August 2009, the European commission has approved Novartis production of Afinitor (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC), the European society of medical oncology, Europe urinary tumor urogenital group (EAU), Spain (SOGUG), the European organization for research and treatment of cancer (EORTC), the European medical oncology (ESMO) treatment guidelines and British consensus guidelines and several European authority guidelines updated, recommend Afinitor as second-line treatment in patients with advanced kidney cancer drugs.
|Chemical Properties||Off White Solid|
|Usage||Macrolide immunosuppressant; derivative of Rapamycin. Inhibits cytokine-mediated lymphocyte proliferation|
|Usage||Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM|
|Usage||Everolimus Macrolide immunosuppressant; Everolimus is a derivative of Rapamycin. Everolimus inhibits cytokine-mediated lymphocyte proliferation.|
|Usage||Everolimus is a semi-synthetic macrocyclic lactone prepared from rapamycin by selective alkylation of the 42-hydroxy group with a silyl-protected hydroxyethyl triflate moiety, followed by addition of an ethylhydroxy moiety to provide greater stability and bioavailability. Like all tacrolimus analogues, everolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. Everolimus is extensively cited in the literature with over 2,000 citations.|
|Everolimus Preparation Products And Raw materials|