SU11274 - CAS 658084-23-2
Catalog number: 658084-23-2
Category: Inhibitor
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Molecular Weight:
SU11274 is a selective Met tyrosine kinase inhibitor with IC50 of 10 nM.
crystalline solid
SU 11274; SU-11274.
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1.Dual MET-EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer.
Tang Z;Du R;Jiang S;Wu C;Barkauskas DS;Richey J;Molter J;Lam M;Flask C;Gerson S;Dowlati A;Liu L;Lee Z;Halmos B;Wang Y;Kern JA;Ma PC Br J Cancer. 2008 Sep 16;99(6):911-22. doi: 10.1038/sj.bjc.6604559.
Despite clinical approval of erlotinib, most advanced lung cancer patients are primary non-responders. Initial responders invariably develop secondary resistance, which can be accounted for by T790M-EGFR mutation in half of the relapses. We show that MET is highly expressed in lung cancer, often concomitantly with epidermal growth factor receptor (EGFR), including H1975 cell line. The erlotinib-resistant lung cancer cell line H1975, which expresses L858R/T790M-EGFR in-cis, was used to test for the effect of MET inhibition using the small molecule inhibitor SU11274. H1975 cells express wild-type MET, without genomic amplification (CNV = 1.1). At 2 microM, SU 11274 had significant in vitro pro-apoptotic effect in H1975 cells, 3.9-fold (P = 0.0015) higher than erlotinib, but had no effect on the MET and EGFR-negative H520 cells. In vivo, SU11274 also induced significant tumour cytoreduction in H1975 murine xenografts in our bioluminescence molecular imaging assay. Using small-animal microPET/MRI, SU11274 treatment was found to induce an early tumour metabolic response in H1975 tumour xenografts. MET and EGFR pathways were found to exhibit collaborative signalling with receptor cross-activation, which had different patterns between wild type (A549) and L858R/T790M-EGFR (H1975).
2.Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells.
Usatyuk PV;Fu P;Mohan V;Epshtein Y;Jacobson JR;Gomez-Cambronero J;Wary KK;Bindokas V;Dudek SM;Salgia R;Garcia JG;Natarajan V J Biol Chem. 2014 May 9;289(19):13476-91. doi: 10.1074/jbc.M113.527556. Epub 2014 Mar 14.
Hepatocyte growth factor (HGF) mediated signaling promotes cell proliferation and migration in a variety of cell types and plays a key role in tumorigenesis. As cell migration is important to angiogenesis, we characterized HGF-mediated effects on the formation of lamellipodia, a pre-requisite for migration using human lung microvascular endothelial cells (HLMVECs). HGF, in a dose-dependent manner, induced c-Met phosphorylation (Tyr-1234/1235, Tyr-1349, Ser-985, Tyr-1003, and Tyr-1313), activation of PI3k (phospho-Yp85) and Akt (phospho-Thr-308 and phospho-Ser-473) and potentiated lamellipodia formation and HLMVEC migration. Inhibition of c-Met kinase by SU11274 significantly attenuated c-Met, PI3k, and Akt phosphorylation, suppressed lamellipodia formation and endothelial cell migration. LY294002, an inhibitor of PI3k, abolished HGF-induced PI3k (Tyr-458), and Akt (Thr-308 and Ser-473) phosphorylation and suppressed lamellipodia formation. Furthermore, HGF stimulated p47(phox)/Cortactin/Rac1 translocation to lamellipodia and ROS generation. Moreover, inhibition of c-Met/PI3k/Akt signaling axis and NADPH oxidase attenuated HGF- induced lamellipodia formation, ROS generation and cell migration.
3.A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan in gastric carcinoma.
Yashiro M;Nishii T;Hasegawa T;Matsuzaki T;Morisaki T;Fukuoka T;Hirakawa K Br J Cancer. 2013 Nov 12;109(10):2619-28. doi: 10.1038/bjc.2013.638. Epub 2013 Oct 15.
BACKGROUND: ;Cancer stem cells (CSCs) may be postulated mediators of the chemoresistance. This study aimed to determine an effective signal inhibitor with effects on the proliferation of CSCs in combination with anticancer drugs.;METHODS: ;We used three gastric cancer cell lines and three side population (SP)-enriched CSC cell lines. We examined the combined effects of inhibitors against stemness signals, including c-Met inhibitor SU11274, and five anticancer drugs on the CSC proliferation and mRNA expression of chemoresistance-associated genes.;RESULTS: ;The IC50 of irinotecan in SP-enriched CSC was 10.5 times higher than parent OCUM-2M cells, whereas that of oxaliplatin, taxol, gemcitabine, and 5-fluorouracil was 2.0, 2.8, 2.0, and 1.2, respectively. The SP cell lines had higher expression levels of UGT1A1, ABCG2, and ABCB1 than their parent cell lines. There was a synergistic antiproliferative effect with a combination of SU11274 and SN38 in SP cells, but not other inhibitors. The SU11274 significantly decreased the expression of UGT1A1, but not ABCG2 and ABCB1. The SN38 plus SU11274 group more effectively suppressed in vivo tumour growth by OCUM-2M/SP cells than either group alone.
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CAS 658084-23-2 SU11274

(CAS: 658084-23-2)

SU11274 is a selective Met tyrosine kinase inhibitor with IC50 of 10 nM.

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CAS 658084-23-2 SU11274

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