PMID- 17462572
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20211203
IS  - 1074-5521 (Print)
IS  - 1074-5521 (Linking)
VI  - 14
IP  - 4
DP  - 2007 Apr
TI  - Identification of a small-molecule inhibitor of class Ia PI3Ks with cell-based 
      screening.
PG  - 371-7
AB  - The mammalian target of rapamycin (mTOR) signaling network is central to the 
      regulation of cell growth in response to both growth factors and nutrients. We 
      developed a high-throughput, cell-based assay to identify small-molecule 
      modulators of the mTOR signaling network. One such compound, which we name 
      quinostatin, potently inhibits this network by directly targeting the 
      lipid-kinase activity of the catalytic subunits of class Ia PI3Ks. This study 
      illustrates the power of unbiased, phenotypic screening as a means for 
      illuminating cell circuitry, and resulted in the identification of a chemotype 
      for selective inhibition of the class Ia PI3Ks.
FAU - Yang, Jiong
AU  - Yang J
AD  - Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts 
      Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA.
FAU - Shamji, Alykhan
AU  - Shamji A
FAU - Matchacheep, Sirinya
AU  - Matchacheep S
FAU - Schreiber, Stuart L
AU  - Schreiber SL
LA  - eng
GR  - GM38627/GM/NIGMS NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Chem Biol
JT  - Chemistry & biology
JID - 9500160
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (quinostatin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Catalytic Domain
MH  - Cell Line, Tumor
MH  - Heterocyclic Compounds, 3-Ring/chemistry/*isolation & purification/*pharmacology
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/chemistry/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/metabolism
MH  - Quinolines/chemistry/*isolation & purification/*pharmacology
MH  - Ribosomal Protein S6/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/04/28 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/04/28 09:00
PHST- 2006/11/28 00:00 [received]
PHST- 2007/02/05 00:00 [revised]
PHST- 2007/02/09 00:00 [accepted]
PHST- 2007/04/28 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/04/28 09:00 [entrez]
AID - S1074-5521(07)00071-3 [pii]
AID - 10.1016/j.chembiol.2007.02.004 [doi]
PST - ppublish
SO  - Chem Biol. 2007 Apr;14(4):371-7. doi: 10.1016/j.chembiol.2007.02.004.