title: Novel inhibitors of mTORC1 and mTORC2.
abstract: The PI3K/Akt/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target for therapeutic intervention in this pathway. The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. This review describes progress in the identification of selective and novel inhibitors of mTORC1/2, focusing on the profile of inhibitors that are in clinical development.
authors.affiliation: OSI Pharmaceuticals Inc, Department of Biochemical and Cellular Pharmacology, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. sbhagwat@osip.com
authors.forename: Shripad V
authors.initials: SV
authors.lastname: Bhagwat
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Crew
mesh_terms: D000818:Animals; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C493245:CRTC2 protein, human; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases