PMID- 14617781
OWN - NLM
STAT- MEDLINE
DCOM- 20040728
LR  - 20200930
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 2
IP  - 11
DP  - 2003 Nov
TI  - Potent and selective inhibitors of the Met [hepatocyte growth factor/scatter 
      factor (HGF/SF) receptor] tyrosine kinase block HGF/SF-induced tumor cell growth 
      and invasion.
PG  - 1085-92
AB  - The hepatocyte growth factor/scatter factor (HGF/SF) receptor, Met, mediates 
      various cellular responses on activation with its ligand, including 
      proliferation, survival, motility, invasion, and tubular morphogenesis. Met 
      expression is frequently up-regulated in sarcomas and carcinomas. Experimental 
      evidence suggests that Met activation correlates with poor clinical outcome and 
      the likelihood of metastasis. Therefore, inhibitors of Met tyrosine kinase may be 
      useful for the treatment of a wide variety of cancers that have spread from the 
      primary site. We have discovered potent and selective pyrrole-indolinone Met 
      kinase inhibitors and characterized them for their ability to inhibit 
      HGF/SF-induced cellular responses in vitro. These compounds inhibit 
      HGF/SF-induced receptor phosphorylation in a dose-dependent manner. They also 
      inhibit the HGF/SF-induced motility and invasion of epithelial and carcinoma 
      cells. Therefore, these compounds represent a class of prototype small molecules 
      that selectively inhibit the Met kinase and could lead to identification of 
      compounds with potential therapeutic utility in treatment of cancers.
FAU - Wang, Xueyan
AU  - Wang X
AD  - SUGEN, Inc., South San Francisco, CA, USA. xwang720@yahoo.com
FAU - Le, Phuong
AU  - Le P
FAU - Liang, Congxin
AU  - Liang C
FAU - Chan, Julie
AU  - Chan J
FAU - Kiewlich, David
AU  - Kiewlich D
FAU - Miller, Todd
AU  - Miller T
FAU - Harris, Dave
AU  - Harris D
FAU - Sun, Li
AU  - Sun L
FAU - Rice, Audie
AU  - Rice A
FAU - Vasile, Stefan
AU  - Vasile S
FAU - Blake, Robert A
AU  - Blake RA
FAU - Howlett, Anthony R
AU  - Howlett AR
FAU - Patel, Neela
AU  - Patel N
FAU - McMahon, Gerald
AU  - McMahon G
FAU - Lipson, Kenneth E
AU  - Lipson KE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
CIN - Mol Cancer Ther. 2011 Nov;10(11):2022-3. PMID: 22072807
MH  - Binding Sites
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Hepatocyte Growth Factor/*antagonists & inhibitors/*pharmacology
MH  - Humans
MH  - Indoles/pharmacology
MH  - Models, Molecular
MH  - *Neoplasm Invasiveness
MH  - Neoplasms/drug therapy/*pathology
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/metabolism
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins c-met/*antagonists & inhibitors/chemistry/*metabolism
MH  - Pyrroles/pharmacology
MH  - Signal Transduction/drug effects
EDAT- 2003/11/18 05:00
MHDA- 2004/07/29 05:00
CRDT- 2003/11/18 05:00
PHST- 2003/11/18 05:00 [pubmed]
PHST- 2004/07/29 05:00 [medline]
PHST- 2003/11/18 05:00 [entrez]
PST - ppublish
SO  - Mol Cancer Ther. 2003 Nov;2(11):1085-92.