PMID- 22125084
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20211203
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Print)
IS  - 1064-3745 (Linking)
VI  - 821
DP  - 2012
TI  - Development of ATP-competitive mTOR inhibitors.
PG  - 447-60
LID - 10.1007/978-1-61779-430-8_29 [doi]
AB  - The mammalian Target of Rapamycin (mTOR)-mediated signaling transduction pathway 
      has been observed to be deregulated in a wide variety of cancer and metabolic 
      diseases. Despite extensive clinical development efforts, the well-known 
      allosteric mTOR inhibitor rapamycin and structurally related rapalogs have failed 
      to show significant single-agent antitumor efficacy in most types of cancer. This 
      limited clinical success may be due to the inability of the rapalogs to maintain 
      a complete blockade mTOR-mediated signaling. Therefore, numerous efforts have 
      been initiated to develop ATP-competitive mTOR inhibitors that would block both 
      mTORC1 and mTORC2 complex activity. Here, we describe our experimental approaches 
      to develop Torin1 using a medium throughput cell-based screening assay and 
      structure-guided drug design.
FAU - Liu, Qingsong
AU  - Liu Q
AD  - Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA.
FAU - Kang, Seong A
AU  - Kang SA
FAU - Thoreen, Carson C
AU  - Thoreen CC
FAU - Hur, Wooyoung
AU  - Hur W
FAU - Wang, Jinhua
AU  - Wang J
FAU - Chang, Jae Won
AU  - Chang JW
FAU - Markhard, Andrew
AU  - Markhard A
FAU - Zhang, Jianming
AU  - Zhang J
FAU - Sim, Taebo
AU  - Sim T
FAU - Sabatini, David M
AU  - Sabatini DM
FAU - Gray, Nathanael S
AU  - Gray NS
LA  - eng
GR  - R01 AI047389/AI/NIAID NIH HHS/United States
GR  - R01 CA103866/CA/NCI NIH HHS/United States
GR  - R01 CA129105/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
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 (CRTC2 protein, human)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Naphthyridines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - *Drug Design
MH  - HEK293 Cells
MH  - High-Throughput Screening Assays/*methods
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Multiprotein Complexes
MH  - Naphthyridines/*chemistry/pharmacology
MH  - Protein Kinase Inhibitors/*chemistry/pharmacology
MH  - Proteins/*antagonists & inhibitors
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/*antagonists & inhibitors
PMC - PMC3964610
MID - NIHMS570841
EDAT- 2011/11/30 06:00
MHDA- 2012/03/17 06:00
PMCR- 2014/03/25
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]
PHST- 2014/03/25 00:00 [pmc-release]
AID - 10.1007/978-1-61779-430-8_29 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2012;821:447-60. doi: 10.1007/978-1-61779-430-8_29.