PMID- 22059905
OWN - NLM
STAT- MEDLINE
DCOM- 20130221
LR  - 20211203
IS  - 1000-467X (Print)
IS  - 1944-446X (Electronic)
IS  - 1944-446X (Linking)
VI  - 31
IP  - 1
DP  - 2012 Jan
TI  - Current development of the second generation of mTOR inhibitors as anticancer 
      agents.
PG  - 8-18
LID - 10.5732/cjc.011.10281 [doi]
AB  - The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts 
      as a "master switch" for cellular anabolic and catabolic processes, regulating 
      the rate of cell growth and proliferation. Dysregulation of the mTOR signaling 
      pathway occurs frequently in a variety of human tumors, and thus, mTOR has 
      emerged as an important target for the design of anticancer agents. mTOR is found 
      in two distinct multiprotein complexes within cells, mTORC1 and mTORC2. These two 
      complexes consist of unique mTOR-interacting proteins and are regulated by 
      different mechanisms. Enormous advances have been made in the development of 
      drugs known as mTOR inhibitors. Rapamycin, the first defined inhibitor of mTOR, 
      showed effectiveness as an anticancer agent in various preclinical models. 
      Rapamycin analogues (rapalogs) with better pharmacologic properties have been 
      developed. However, the clinical success of rapalogs has been limited to a few 
      types of cancer. The discovery that mTORC2 directly phosphorylates Akt, an 
      important survival kinase, adds new insight into the role of mTORC2 in cancer. 
      This novel finding prompted efforts to develop the second generation of mTOR 
      inhibitors that are able to target both mTORC1 and mTORC2. Here, we review the 
      recent advances in the mTOR field and focus specifically on the current 
      development of the second generation of mTOR inhibitors as anticancer agents.
FAU - Zhou, Hong-Yu
AU  - Zhou HY
AD  - Department of Biochemistry and Molecular Biology, Louisiana State University 
      Health Sciences Center, Shreveport, LA 71130-3932, USA.
FAU - Huang, Shi-Le
AU  - Huang SL
LA  - eng
GR  - R01 CA115414/CA/NCI NIH HHS/United States
GR  - R01 CA115414-04/CA/NCI NIH HHS/United States
GR  - CA115414/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20111104
PL  - England
TA  - Chin J Cancer
JT  - Chinese journal of cancer
JID - 101498232
RN  - 0 
      (1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one)
RN  - 0 
      (4-(2-(dimethylamino)vinyl)-2-(3-hydroxyphenyl)-6-morpholinopyrimidine-5-carbonitrile)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Furans)
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Morpholines)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Naphthyridines)
RN  - 0 (PI103)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Pyridines)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinolines)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - H5669VNZ7V (PP242)
RN  - RUJ6Z9Y0DT (dactolisib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Furans/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Indoles/pharmacology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Morpholines/pharmacology
MH  - Multiprotein Complexes/antagonists & inhibitors
MH  - Naphthyridines/pharmacology
MH  - Neoplasms/*pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Purines/pharmacology
MH  - Pyridines/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Quinolines/pharmacology
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC3249493
MID - NIHMS337502
EDAT- 2011/11/09 06:00
MHDA- 2013/02/22 06:00
PMCR- 2012/01/01
CRDT- 2011/11/09 06:00
PHST- 2011/11/09 06:00 [entrez]
PHST- 2011/11/09 06:00 [pubmed]
PHST- 2013/02/22 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - cjc.011.10281 [pii]
AID - cjc-31-01-008 [pii]
AID - 10.5732/cjc.011.10281 [doi]
PST - ppublish
SO  - Chin J Cancer. 2012 Jan;31(1):8-18. doi: 10.5732/cjc.011.10281. Epub 2011 Nov 4.