PMID- 22125076
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20220311
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 821
DP  - 2012
TI  - Evaluating the therapeutic potential of mTOR inhibitors using mouse genetics.
PG  - 329-47
LID - 10.1007/978-1-61779-430-8_21 [doi]
AB  - Extensive efforts are underway to develop small-molecule inhibitors of the 
      mammalian target of rapamycin (mTOR) kinase. It is hoped that these inhibitors 
      will have widespread clinical impact in oncology because mTOR is a major 
      downstream effector of PI3K signaling, one of the most frequently activated 
      pathways in cancer. In cells, mTOR is the catalytic core subunit of two distinct 
      complexes, mTORC1 and mTORC2, which are defined by unique mTOR-interacting 
      proteins and have unique functions downstream of PI3K. Two classes of mTOR 
      inhibitors are currently being evaluated as cancer therapeutics: rapamycin and 
      its analogs, which partially inhibit mTORC1 and in some cell types mTORC2, and 
      the recently described ATP-competitive inhibitors, which inhibit the kinase 
      activity of both complexes. Although small molecules that selectively target 
      mTORC2 do not yet exist, experiments using mouse genetics suggest that a 
      theoretical mTORC2 inhibitor may have significant therapeutic value. Here, we 
      discuss an approach to model mTOR complex specific inhibitors using mouse 
      genetics and how it can be applied to other gene products involved in oncogenic 
      signaling to which inhibitors do not exist.
FAU - Li, Huawei
AU  - Li H
AD  - Program in Molecular Medicine, University of Massachusetts Medical School, 
      Worcester, MA, USA.
FAU - Cotton, Jennifer L
AU  - Cotton JL
FAU - Guertin, David A
AU  - Guertin DA
LA  - eng
GR  - R00CA129613/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Crtc2 protein, mouse)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenosine Triphosphate/chemistry/metabolism
MH  - Animals
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Drug Discovery
MH  - *Gene Knockout Techniques
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - PTEN Phosphohydrolase/antagonists & inhibitors/genetics
MH  - Prostatic Neoplasms/*drug therapy/genetics
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Signal Transduction/genetics
MH  - Sirolimus/analogs & derivatives
MH  - Trans-Activators/*antagonists & inhibitors
MH  - Transcription Factors
EDAT- 2011/11/30 06:00
MHDA- 2012/03/17 06:00
CRDT- 2011/11/30 06:00
PHST- 2011/11/30 06:00 [entrez]
PHST- 2011/11/30 06:00 [pubmed]
PHST- 2012/03/17 06:00 [medline]
AID - 10.1007/978-1-61779-430-8_21 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2012;821:329-47. doi: 10.1007/978-1-61779-430-8_21.