There are three commercially available mTOR Inhibitors (mammalian (mechanistic) target of rapamycin inhibitors) approved by the U.S. Food and Drug Administration (FDA) approved, such as sirolimus, everolimus, and temsirolimus. Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase which senses variety of environmental cues, such as glucose, oxygen, lipids, amino acids, cytokines, and growth factors, and integrates these signals to orchestrate cell growth, proliferation, and differentiation. mTOR is serine-threonine protein kinase present in all eukaryotic organisms. The roles of mTOR in the development and regulation of immune system have been rapidly emerging.
mTOR Inhibitors are a new class of immunosuppressants. In contrast to other macrolides, such as cyclosporine A and tacrolimus, they do not inhibit calcineurin and thereby signal I of T-cell activation. mTOR inhibitors block the activity of the mammalian target of rapamycin. It is a protein kinase, which regulates growth factors that stimulate cell growth and angiogenesis. The mTOR, mTORC1 and mTORC2, is the major regulator of growth in animals and controls most anabolic and catabolic processes in response to nutrients and nutrient-induced signals, such as insulin. mTOR is activated by amino acids, insulin, and growth factors, & impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR Inhibitors also have a wide range of applications, including targeted therapy for cancer, organ transplants, and rheumatoid arthritis. In addition to inhibiting tumor cell proliferation, mTOR also regulates cellular metabolism. Abnormally activated mTOR stimulates tumor cell proliferation, invasion, and metastasis. mTORC1 pathway is activated by the PI3K/phosphate and fungi homology deletion on chromosome 10 (PTEN) gene. Many malignancies arise from genetic mutations in this pathway. In tumors, altered PTEN expression can lead to tumor cells that suppress the immune system. In muscles, mTORC1 play crucial role in regulating protein synthesis, mitochondrial biogenesis, and oxidative metabolism. Muscle contractions increase mTORC1 activity. mTOR Inhibitors is a protein that helps control several cell functions, including cell division and survival, and binds to rapamycin and other drugs. In certain cancers, mTOR pathway is more active. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays a vital role in tumor metabolism. It may be more active in some types of cancer cells than it is in normal cells. Blocking mTOR may cause the cancer cells to die. It is a type of serine/threonine protein kinase. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass. mTOR inhibitors (Mammalian target of rapamycin inhibitors) are used in treatment of renal cancer and is being studied for use in other types of cancers. More benefits are being seen when mTOR Inhibitors are combined with other chemotherapy agents. mTOR pathway is a central regulator of mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white & brown adipose tissue, and the brain, and is dysregulated in human diseases, such as depression, obesity, diabetes, and certain cancers. mTOR inhibitors provides more benefits when used with chemotherapy agents to treat cancers.
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