-
外観
白色〜褐色, 結晶性粉末〜粉末
-
溶解性
メタノール溶状：試験適合
-
用途
FK506 の構造類似体であ
り、FK506 と同様に FK506 結合タンパク質
（FKBP）と結合しますが、FK506 とは異なり、
カルシニューリンの活性は阻害しません。ラ
パマイシンと FKBP の複合体は mTOR に結
合し、mTOR のキナーゼ活性を阻害すること
により、IL-2 からのシグナルを阻害します。
-
用途
移植臓器拒絶の予防のため、リンパ脈管筋腫症の治療のために医学分野で使われている。ヒトにおいて免疫抑制機能を持ち、腎臓移植の拒絶の予防において特に有用である。インターロイキン-2（IL-2）の産生を低下させることによってT細胞およびB細胞の活性化を阻害する。冠動脈ステント（英語版）のコーティング剤としても使われている。
-
効能
抗悪性腫瘍薬, 免疫抑制薬, mTOR阻害薬
-
商品名
ラパリムス (ノーベルファーマ); ラパリムス (ノーベルファーマ)
-
化学的特性
White to Off-White Solid
-
天然物の起源
Rapamycin was first discovered in 1972 in the soil of Easter Island produced by a bacterium called Streptomyces hygroscopicus. It takes its name from Rapa Nui, the indigenous name for the island. It is known clinically as sirolimus or Rapamune.
-
使用
Labelled Rapamycin. A triene macrolide antibiotic isolated from Streptomyces hygroscopicus. Name derived from the native word for Easter Island, Rapa?Nui. Used as an immunosuppressant; antirestenotic. This compound contains aproximately 2% d0.;Labeled Sir
-
適応症
Mechanistic target of rapamycin (mTOR) is a serine/threonine-specific protein kinase in the PI3/PI4-kinase family. mTOR was named after the natural macrolide rapamycin, also known as sirolimus, which was isolated from a soil sample from Easter Island in the 1970s and later evaluated as an immunosuppressive agent. The anticancer activity of rapamycin was discovered in the 1980s, although the mechanismof action and the identification of the rapamycin target, mTOR, were not elucidated until the 1990s. Rapamycin and its macrocyclic analogues, such as temsirolimus (Torisel(R), Wyeth/Pfizer) and everolimus (Afinitor(R), Novartis), are grouped as “rapalogs” that constitute the first-generation mTOR inhibitors.
Rapamycin was approved by the US FDA in 1999 as an immunosuppressive agent to prevent organ rejection in patients receiving kidney transplants. Although a large number of clinical studies have been performed to evaluate the anticancer activities of sirolimus in different types of cancers, such as invasive bladder cancer, breast cancer, and leukemia, most studies show limited efficacy. Outside oncological indications, sirolimus was approved by FDA for the treatment of a rare progressive lung disease lymphangioleiomyomatosis in 2015. Temsirolimus was approved for the treatment of advanced RCC. Everolimus was approved in the EU for the prevention of organ rejection in heart and kidney transplant recipients before FDA approved it in 2009 for the treatment of advanced RCC resistant to sunitinib or sorafenib and for the treatment of advanced or metastatic gastrointestinal and lung tumors in 2016. Additionally, rapamycin and rapalogs are being investigated as antiaging therapeutics or for the treatment of age-related diseases. Studies have revealed that mTOR activity can be retained under hypoxic conditions via mutations in the PI3K pathway, leading to increased translation and hypoxic gene expression and tumor progression.
-
定義
ChEBI: A macrolide isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.
-
一般的な説明
Rapamycin is an anti-fungal antibiotic isolated from Streptomyces hygroscopicus. This antibiotic is active against all strains of Candida albicans. It blocks the signal transduction pathways required for the activation of T-helper cells.
-
生物活性
Antifungal and immunosuppressant. Specific inhibitor of mTOR (mammalian target of Rapamycin). Complexes with FKBP-12 and binds mTOR inhibiting its activity. Inhibits interleukin-2-induced phosphorylation and activation of p70 S6 kinase.
