-
外観
白色～うすい褐色、結晶性粉末～粉末
-
溶解性
エタノール及びアセトンに溶け、水にほとんど溶けない。
-
用途
細胞内 で FKBP12 と 複 合
体 を 形 成 し、mTOR（mammalian target of
rapamycin）を選択的に阻害します。
-
用途
ラパマイシンの誘導体であり、
mTOR 阻害剤です。FK506 結合タンパク質
-12（FKBP-12）と結合して mTOR の活性を
阻害することにより、腫瘍細胞のシグナル伝
達を阻害し、腫瘍細胞の増殖を抑制する、ま
た、腫瘍細胞からの VEGF の産生と VEGF に
よる血管内皮細胞の増殖を抑制し、血管新生
を抑制すると考えられています。
-
効能
抗悪性腫瘍薬, 免疫抑制薬, mTOR阻害薬
-
商品名
アフィニトール (ノバルティスファーマ); アフィニトール (ノバルティスファーマ); サーティカン (ノバルティスファーマ)
-
説明
Everolimus, an oral immunosuppressant for the treatment of kidney and heart transplant rejection, is the 40-O-(2-hydroxyethyl) derivative of rapamycin. It has immunosuppressive properties similar to those of rapamycin, but with improved pharmacokinetic profile. Everolimus, like rapamycin, is a proliferation signal inhibitor that exerts its immunosuppressive effect by inhibiting the activation of p70 S6 kinase, thereby blocking growth factor-driven proliferation of T cells, B cells and vascular smooth muscle cells, and arresting cell cycle at the G1 phase. Inhibition of p70 S6 kinase activation by everolimus and rapamycin is mediated by their binding to FKBP12 (FK506 binding-protein 12). Everolimus inhibits FK506 binding to FKBP12 with an IC50 of 1.8–2.6 nM, and it is about 3- to 5-fold less potent than rapamycin (IC50=0.4–0.9 nM). The in vitro immunosuppressive activity of everolimus is also slightly less than that of rapamycin as demonstrated in a mixed lymphocyte reaction (MLR) assay (IC50=0.2–1.6 nM versus 0.07–0.5 nM, respectively) and in antigen-specific human helper T-cell clones (IC50=0.05–0.17nM versus 0.014–0.37nM, respectively). However, the in vivo immunosuppressive activity of oral everolimus 1–5 mg/ kg/day is similar to that of rapamycin at equivalent doses in rat models of renal or cardiac transplantation, localized graft-versus-host disease, and autoimmune glomerulonephritis. The recommended dosage of everolimus is 0.75 mg twice daily, and it is used in combination with cyclosporine microemulsion and corticosteroids.
-
化学的特性
Off White Solid
-
使用
Everolimus (IX) (SDZ-RAD), was developed by
Novartis as an immunosuppressant to be used in
conjunction with cyclosporin in transplantation allograft
rejection and was recently approved in the US in 2003.
Another natural product that had been approved for use in
transplantation is rapamycin (sirolimus) as an inejectable
agent. In an attempt to develop an orally bioavailable immunosuppressant agent, many companies attempted
modification of rapamycin itself.
-
定義
ChEBI: Everolimus is a macrocyclic lactone that is rapamycin in which the hydroxy group attached to the cyclohexyl moiety has been converted into the corresponding 2-hydroxyethyl ether. It is an immunosuppressant and antineoplastic agent. It has a role as an antineoplastic agent, an immunosuppressive agent, a mTOR inhibitor, an anticoronaviral agent and a geroprotector. It is a primary alcohol, a secondary alcohol, an ether, a cyclic ketone, a cyclic acetal and a macrolide lactam. It is functionally related to a member of sirolimus.
-
一般的な説明
Everolimus, sold under trade names including Zortress?, Certican, and Afinitor?, is an immunosuppressant drug used to prevent rejection of organ transplants and to treat renal cell cancer and other tumors. This Certified Spiking Solution? is suitable as starting material for calibrators, controls, or linearity standards for therapeutic drug monitoring or clinical and diagnostic testing of everolimus in patient whole blood samples by LC-MS/MS.
