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Sirolimus (INN/USAN), also known as rapamycin, is a macrolide (one of a group of drugs containing a macrolide ring) produced by the bacterium ''Streptomyces hygroscopicus''. It has immunosuppressant functions in humans and is used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B cells by inhibiting the production of interleukin-2 (IL-2). Sirolimus is also used as a coronary stent coating. Sirolimus was isolated for the first time in 1972 by Suren Sehgal and colleagues from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui.〔 Sirolimus was initially developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and antiproliferative properties due to its ability to inhibit mTOR. It has since been shown to prolong the life of mice and might also be useful in the treatment of certain cancers. It was approved by the US Food and Drug Administration in September 1999 and is marketed under the trade name Rapamune by Pfizer (formerly by Wyeth). ==Mechanism of action== Unlike the similarly named tacrolimus, sirolimus is not a calcineurin inhibitor, but it has a similar suppressive effect on the immune system. Sirolimus inhibits IL-2 and other cytokines receptor-dependent signal transduction mechanisms, via action on mTOR, and thereby blocks activation of T and B cells. Tacrolimus and cyclosporine inhibit the secretion of IL-2, by inhibiting calcineurin. The mode of action of sirolimus is to bind the cytosolic protein FK-binding protein 12 (FKBP12) in a manner similar to tacrolimus. Unlike the tacrolimus-FKBP12 complex, which inhibits calcineurin (PP2B), the sirolimus-FKBP12 complex inhibits the mTOR (mechanistic (formerly mammalian) Target Of Rapamycin, rapamycin being another name for sirolimus) pathway by directly binding to mTOR Complex 1 (mTORC1). mTOR has also been called FRAP (FKBP-rapamycin-associated protein), RAFT (rapamycin and FKBP target), RAPT1, or SEP. The earlier names FRAP and RAFT were coined to reflect the fact that sirolimus must bind FKBP12 first, and only the FKBP12-sirolimus complex can bind mTOR. However, mTOR is now the widely accepted name, since Tor was first discovered via genetic and molecular studies of sirolimus-resistant mutants of ''Saccharomyces cerevisiae'' that identified FKBP12, Tor1, and Tor2 as the targets of sirolimus and provided robust support that the FKBP12-sirolimus complex binds to and inhibits Tor1 and Tor2. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「sirolimus」の詳細全文を読む スポンサード リンク
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