Everolimus is a derivative of sirolimus, also known as 40-O-(2-hydroxyethyl)-rapamycin, or 40-O-(2-hydroxyethyl)-sirolimus, A kinase drug that interferes with cell communication to prevent tumor cell growth. It is an oral mammalian rapamycin (mTOR) inhibitor that has been used clinically to prevent rejection after kidney transplantation and heart transplantation. It can also be used to treat patients with advanced renal cell carcinoma who have used two inhibitory vascular endothelial growth factor receptor kinase inhibitors: sutentibine (Pfizer) and sorafenib (Nexavar, Bayer Pharmaceuticals). The side effects are mild.
Sunitinib and sorafenib are multiple kinase inhibitors (acting on multiple cellular targets), while everolimus blocks specific proteins in mammalian rapamycin targets (mTOR), interfering with Growth, differentiation and metabolism of cancer cells. This mTOR pathway regulates abnormalities in some human tumors. Everolimus binds to the intracellular protein FKBP-12 to form an inhibitory complex, thereby inhibiting mTOR kinase activity, while reducing the downstream effector of mTOR, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E) -BP) activity. In addition, everolimus inhibits the expression of hypoxia-inducible factors (such as HIF-1) and decreases the expression of vascular endothelial growth factor (VEGF), both in vitro and in vivo studies have shown that cell proliferation, angiogenesis and glucose uptake can be reduced.