Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 6, Pages -Publisher
MDPI AG
DOI: 10.3390/ijms17060975
Keywords
mTOR inhibitor; kidney; renal cancer; diabetic nephropathy; kidney transplantation
Funding
- Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT) [15K18922, 15H04666]
- Funding Program for Next Generation World-Leading Researchers (NEXT Program) [LS073]
- Council for Science and Technology Policy of the Japan Society for the Promotion of Science of Japan
- Grants-in-Aid for Scientific Research [26670081, 15K18922, 15H04666] Funding Source: KAKEN
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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.
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