title: Role of mTOR Inhibitors in Kidney Disease.
abstract: 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.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. motokaji@jsd.med.kyushu-u.ac.jp.
authors.forename: Moto
authors.initials: M
authors.lastname: Kajiwara
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. satomsdb@pharm.med.kyushu-u.ac.jp.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: diabetic nephropathy; kidney; kidney transplantation; mTOR inhibitor; renal cancer