mTOR Inhibitors
The mechanistic target of rapamycin (mTOR), a serine/threonine-specific protein kinase that is a member of the phosphatidylinositol-3 kinase (PI3K) related kinase family, is inhibited by a class of medications known as mTOR inhibitors (PIKKs). Two protein complexes, mTORC1, and mTORC2, which mTOR forms and signals through, control cellular metabolism, growth, and proliferation. The so-called rapalogs (rapamycin and its analogs), which have demonstrated tumor responses in human studies against a variety of tumor types, are the most well-established mTOR inhibitors.
mTOR inhibitors of the first generation
Rapamycin’s reintroduction as an anticancer drug started with the discovery of temsirolimus in the 1990s (CCI-779). The toxicological profile of this brand-new soluble rapamycin derivative in animals was good. Since then, new rapamycin derivatives with improved pharmacokinetics and fewer immunosuppressive side effects have been developed for the treatment of cancer. These rapalogs include temsirolimus (CCI-779), everolimus (RAD001), and ridaforolimus, which are being examined in cancer clinical studies (AP-23573). Comparable therapeutic advantages to rapamycin are provided by rapamycin analogs. The National Cancer Institute published a list of more than 200 clinical research in 2012 that investigated the anticancer potential of rapalogs as a monotherapy or component of combination therapy for various cancer types. First-generation mTOR inhibitors known as rapalogs are effective in a range of preclinical conditions. Rapalogs are insufficient for generating a broad and powerful anticancer impact, at least when used as monotherapy, due to the previously mentioned restricted mTOR inhibition.
mTOR Signaling Pathway
Cell signaling (cell communication in British English) is the capacity of a cell to receive, process, and transmit messages with its surroundings and with itself. Cell signaling is a basic characteristic of all prokaryotic and eukaryotic cellular life. Cell signaling can take place across short or long distances, and is thus classed as autocrine, juxtacrine, paracrine, and endocrine. Signaling molecules can be produced via a variety of biosynthetic pathways and released by passive or active transporters, as well as cell injury.
Receptors are important in cell signaling because they can sense chemical signals as well as physical inputs. Receptors are proteins that are found on the cell surface or within the cell’s interior, such as the cytoplasm, organelles, and nucleus. Additional enzymatic activity such as proteolytic cleavage, phosphorylation, methylation, and ubiquitinylation may occur as a result of these signaling pathways. Each cell is designed to respond to certain extracellular signal molecules, which serve as the foundation for development, tissue repair, immunology, and homeostasis.