MTOR and mTOR inhibitors

mTOR (mammalian target of rapamycin) is one of the important proteins of the signaling cascade. It is a serine/threonine kinase that consists of 2549 amino acids, which corresponds to 289 kDa. In mammals, this protein occurs as mTORC1 (mTOR complex 1) and as mTORC2 (mTOR complex 2).

Function

For example, mTOR is used incell growth and cell survival, it affects metabolic pathways (e.g. for insulin) and, last but not least, molecules used in signal propagation in the cell (growth factors, hormones). Functionally, it is part of the phosphatidylinositol 3-kinase (PI3K) family of enzymes due to its homologous C-terminus as that of PI3K. It is thus closely linked to the PI3K-AKT and Ras-ERK pathways. It regulates the translation of initiation factor 4G (or eIF4G) as well as ribosomal 40S S6 kinase (S6K1/S6K2). Disorders of this protein are thought to be associated with diabetes mellitus and various cancers. náhled|mTOR signální dráha

mTOR signaling pathway

mTOR inhibitors

The best-known representative is rapamycin (sirolism) , which was originally administered as an immunosuppressant used after transplants, but is now indicated especially for kidney carcinomas Chemically, it is a low molecular weight macrolide antibiotic produced by bacteria of the genus Streptomyces. Other representatives include everolimus and temsirolimus. NThe most common indication for the use of mTOR inhibitors is various types of cancer (that is, they serve as cytostatics), but the effect of these molecules on certain neurodegenerative diseases is also being intensively investigated. náhled|Sirolimus

Mechanism of action of mTOR inhibitors

By inhibiting mTOR, the synthesis of cyclin D is limited (the cell is stopped in the G1 phase of the cell cycle) and HIF-1a (as a result, VEGF is not expressed, which would induce neoangiogenesis).

Links

Related Articles

• Cytostasis
• Antitumor therapy
• Cell signaling

Sirolimus

Resources

• JIŘINA, Martínková – AND A COLLECTIVE,. Farmakologie : pro studenty zdravotnických oborů, 2., zcela přepracované a doplněné vydání. - edition. Grada Publishing a.s., 2018. ISBN 978-80-271-0929-6.

• AYLETT, Christopher H. S. Architecture of human mTOR complex 1 [online]. ©2016. [cit. 2022-02-26]. <https://www.science.org/doi/abs/10.1126/science.aaa3870>.

• CASTELLANOS, Mar. Mammalian Target of Rapamycin [online]. ©2016. [cit. 2022-02-26]. <https://www.sciencedirect.com/topics/neuroscience/mammalian-target-of-rapamycin>.

• LAPLANTE, Mathieu. mTOR signaling at a glance [online]. ©2009. [cit. 2022-02-26]. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758797/>.