Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors

Med Res Rev. 2019 Mar;39(2):631-664. doi: 10.1002/med.21535. Epub 2018 Sep 24.

Abstract

The mechanistic/mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin, regulates many normal cell processes such as transcription, cell growth, and autophagy. Overstimulation of mTOR by its ligands, amino acids, sugars, and/or growth factors leads to physiological disorders, including cancer and neurodegenerative diseases. In this study, we reviewed the recent advances regarding the mechanism that involves mTOR in cancer, aging, and neurodegenerative diseases. The chemical and biological properties of recently reported small molecules that function as mTOR kinase inhibitors, including adenosine triphosphate-competitive inhibitors and dual mTOR/PI3K inhibitors, have also been reviewed. We focused on the reports published in the literature from 2012 to 2017.

Keywords: PI3K; aging; anticancer; kinase inhibitors; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Animals
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Melanoma / metabolism
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Skin Neoplasms / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Ligands
  • Protein Kinase Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases