Role of mTOR Inhibitors in Kidney Disease.
Role of mTOR Inhibitors in Kidney Disease.
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DOI：
10.3390/ijms17060975
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发表时间：
2016-06-21
影响因子：
5.6
通讯作者：
Masuda S
中科院分区：
文献类型：
--
作者：
Kajiwara M;Masuda S
第一种抑制哺乳动物雷帕霉素靶蛋白（mTOR）的化合物西罗莫司（雷帕霉素）是在20世纪70年代作为复活节岛（Rapa Nui）收集的土壤细菌代谢物发现的。由于西罗莫司显示出抗增殖活性，研究人员研究了其分子靶点，并确定了TOR1和TOR2。mTOR由mTOR复合物1（mTORC 1）和mTORC 2组成。雷帕莫司类似物包括西罗莫司、依维莫司和替西罗莫司主要对mTORC 1发挥作用，而它们对mTORC 2的抑制作用是温和的。为了获得具有更有效的抗增殖作用的化合物，已经开发了靶向mTORC 1和mTORC 2的mTOR的ATP竞争性抑制剂，并在临床试验中作为抗癌药物进行了测试。目前，mTOR抑制剂被用作针对几种实体瘤的抗癌药物和用于各种器官移植的免疫抑制剂。本文综述了mTOR抑制剂在肾脏疾病中的作用，特别关注肾癌、糖尿病肾病和肾移植。
The first compound that inhibited the mammalian target of rapamycin (mTOR), sirolimus (rapamycin) was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui). Because sirolimus showed antiproliferative activity, researchers investigated its molecular target and identified the TOR1 and TOR2. The mTOR consists of mTOR complex 1 (mTORC1) and mTORC2. Rapalogues including sirolimus, everolimus, and temsirolimus exert their effect mainly on mTORC1, whereas their inhibitory effect on mTORC2 is mild. To obtain compounds with more potent antiproliferative effects, ATP-competitive inhibitors of mTOR targeting both mTORC1 and mTORC2 have been developed and tested in clinical trials as anticancer drugs. Currently, mTOR inhibitors are used as anticancer drugs against several solid tumors, and immunosuppressive agents for transplantation of various organs. This review discusses the role of mTOR inhibitors in renal disease with a particular focus on renal cancer, diabetic nephropathy, and kidney transplantation.