Mapping of mTOR drug targets: Featured platforms for anti-cancer drug discovery

The mammalian/mechanistic target of rapamycin (mTOR) is a regulatory protein kinase involved in cell growth and proliferation. mTOR is usually assembled in two different complexes with different regulatory mechanisms, mTOR complex 1 (mTORC1 ) and mTORC2, which are involved in different functions such as cell proliferation and cytoskeleton assembly, respectively. In cancer cells, mTOR is hyperactivated in response to metabolic alterations and/or oncogenic signals to overcome the stressful microenvironments. Therefore, recent research progress for mTOR inhibition involves a variety of compounds that have been developed to disturb the metabolic processes of cancer cells through mTOR inhibition. In addition to competitive or allosteric inhibition, a new inhibition strategy that emerged mTOR complexes destabilization has recently been a concern. Here, we review the history of mTOR and its inhibition, along with the timeline of the mTOR inhibitors. We also introduce prospective drug targets to inhibit mTOR by disrupting the complexation of the components with peptides and small molecules. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

mTOR is a protein kinase involved in cell growth and proliferation, which can be assembled into mTORC1 and mTORC2 complexes with different functions. In cancer cells, mTOR is hyperactivated to adapt to stress conditions, leading to efforts in developing compounds to inhibit mTOR and disrupt cancer cell metabolism.