TY - JOUR
T1 - Role of mTOR inhibitors in kidney disease
AU - Kajiwara, Moto
AU - Masuda, Satohiro
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research (KAKENHI) (15K18922 to M.K., 15H04666 to S.M.) from the Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT) 501100001700 and by the Funding Program for Next GenerationWorld-Leading Researchers (NEXT Program: LS073 to SM) initiated by the Council for Science and Technology Policy of the Japan Society for the Promotion of Science of Japan.
Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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.
AB - 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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U2 - 10.3390/ijms17060975
DO - 10.3390/ijms17060975
M3 - Review article
C2 - 27338360
AN - SCOPUS:84975849741
SN - 1661-6596
VL - 17
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 975
ER -
