Role of mTOR Inhibitors in Kidney Disease
نویسندگان
چکیده
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.
منابع مشابه
P162: Emerging Perspectives on Mtor-Associated Inflammation in Neurodegenerative Diseases
Inflammatory processes have been shown to be involved in development and progression of neurodegenerative diseases. Mammalian target of rapamycin (mTOR) involves in various cellular processes including autophagy, apoptosis and energy metabolism. Recently, studies have been shown an association between mTOR pathway and inflammation, supporting the role of the pathway in the pathogenesis of infla...
متن کاملPI3K and mTOR inhibitor, NVP-BEZ235, is more toxic than X-rays in prostate cancer cells
Background: Radiotherapy and adjuvant androgen deprivation therapy have historically been the first treatment choices for prostate cancer but treatment resistance often limits the capacity to effectively manage the disease. Therefore, alternative therapeutic approaches are needed. Here, the efficacies of radiotherapy and targeting the pro-survival cell signaling components epidermal growth fact...
متن کاملThe role of the mammalian target of rapamycin (mTOR) in renal disease.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a pivotal role in mediating cell size and mass, proliferation, and survival. mTOR has also emerged as an important modulator of several forms of renal disease. mTOR is activated after acute kidney injury and contributes to renal regeneration and repair. Inhibition of mTOR with rapamycin delays recovery of renal fun...
متن کاملPI3K/Akt/mTOR and CDK4 combined inhibition enhanced apoptosis of thyroid cancer cell lines
Introduction Thyroid cancer is a malignant disease with poor prognosis. The PI3K/Akt/mTOR and Cyclin-Dependent Kinase 4 (CDK4) pathways are vital regulators of tumor cell proliferation and survival. Therefore the present study was designed to use dual inhibition of such pathways to kill thyroid cancer cells. Methods and materials The effects of each inhibitors on human ATC and...
متن کاملmTOR inhibitors in the pharmacologic management of tuberous sclerosis complex and their potential role in other rare neurodevelopmental disorders
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder that affects multiple organ systems throughout the body. Dysregulation of the mammalian target of rapamycin (mTOR) pathway is implicated in the disease pathology, and evidence exists to support the use of mTOR inhibitors in treatment. The mTOR pathway has also been investigated as a potential treatment target for sev...
متن کامل