PMID- 19825801
OWN - NLM
STAT- MEDLINE
DCOM- 20100112
LR  - 20200930
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 8
IP  - 10
DP  - 2009 Oct
TI  - GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic 
      lymphoma kinase and shows antitumor activity in experimental models of human 
      cancers.
PG  - 2811-20
LID - 10.1158/1535-7163.MCT-09-0423 [doi]
AB  - The insulin-like growth factor-I receptor (IGF-IR) signaling pathway is activated 
      in various tumors, and inhibition of IGF-IR kinase provides a therapeutic 
      opportunity in these patients. GSK1838705A is a small-molecule kinase inhibitor 
      that inhibits IGF-IR and the insulin receptor with IC(50)s of 2.0 and 1.6 nmol/L, 
      respectively. GSK1838705A blocks the in vitro proliferation of cell lines derived 
      from solid and hematologic malignancies, including multiple myeloma and Ewing's 
      sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the 
      inhibitory effect of GSK1838705A on insulin receptor, minimal effects on glucose 
      homeostasis were observed at efficacious doses. GSK1838705A also inhibits the 
      anaplastic lymphoma kinase (ALK), which drives the aberrant growth of anaplastic 
      large-cell lymphomas, some neuroblastomas, and a subset of non-small cell lung 
      cancers. GSK1838705A inhibits ALK, with an IC(50) of 0.5 nmol/L, and causes 
      complete regression of ALK-dependent tumors in vivo at well-tolerated doses. 
      GSK1838705A is therefore a promising antitumor agent for therapeutic use in human 
      cancers.
FAU - Sabbatini, Peter
AU  - Sabbatini P
AD  - Oncology R&D, Cancer Research, GlaxoSmithKline, 1250 South Collegeville Road, 
      Collegeville, PA 19426, USA.
FAU - Korenchuk, Susan
AU  - Korenchuk S
FAU - Rowand, Jason L
AU  - Rowand JL
FAU - Groy, Arthur
AU  - Groy A
FAU - Liu, Qi
AU  - Liu Q
FAU - Leperi, Dominic
AU  - Leperi D
FAU - Atkins, Charity
AU  - Atkins C
FAU - Dumble, Melissa
AU  - Dumble M
FAU - Yang, Jingsong
AU  - Yang J
FAU - Anderson, Kelly
AU  - Anderson K
FAU - Kruger, Ryan G
AU  - Kruger RG
FAU - Gontarek, Richard R
AU  - Gontarek RR
FAU - Maksimchuk, Kenneth R
AU  - Maksimchuk KR
FAU - Suravajjala, Sapna
AU  - Suravajjala S
FAU - Lapierre, Russell R
AU  - Lapierre RR
FAU - Shotwell, J Brad
AU  - Shotwell JB
FAU - Wilson, Joseph W
AU  - Wilson JW
FAU - Chamberlain, Stanley D
AU  - Chamberlain SD
FAU - Rabindran, Sridhar K
AU  - Rabindran SK
FAU - Kumar, Rakesh
AU  - Kumar R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (GSK 1838705A)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Alk protein, mouse)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Blood Glucose/metabolism
MH  - Cell Proliferation/drug effects
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism
MH  - Pyrimidines/*pharmacology
MH  - Pyrroles/*pharmacology
MH  - Receptor Protein-Tyrosine Kinases
MH  - Receptor, IGF Type 1/*antagonists & inhibitors/metabolism
MH  - Receptor, Insulin/metabolism
MH  - Signal Transduction/drug effects
MH  - *Xenograft Model Antitumor Assays
EDAT- 2009/10/15 06:00
MHDA- 2010/01/13 06:00
CRDT- 2009/10/15 06:00
PHST- 2009/10/15 06:00 [entrez]
PHST- 2009/10/15 06:00 [pubmed]
PHST- 2010/01/13 06:00 [medline]
AID - 8/10/2811 [pii]
AID - 10.1158/1535-7163.MCT-09-0423 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2009 Oct;8(10):2811-20. doi: 10.1158/1535-7163.MCT-09-0423.