Catalog Number: 2693
Chemical Name: (2R)-1-[[5-[(Z)-[5-[[(2,6-Dichlorophenyl)methyl]sulfonyl]-1,2-dihydro-2-oxo-3H-indol-3-ylidene]methyl]-2,4-dimethyl-1H-pyrrol-3-yl]carbonyl]-2-(1-pyrrolidinylmethyl)pyrrolidine
Biological Activity
Potent, selective and ATP-competitive inhibitor of MET kinase (IC50 values are 9, 68, 200, 1400, 3000, 3800 and 6000 nM for MET, Ron, Flk-1, c-abl, FGFR1, EGFR and c-src respectively and > 10000 nM for IGF-IR, PDGFR, AURORA2, PKA, PKBα, p38α, MK2 and MK3). Antitumor agent; inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts.
Technical Data
  • M.Wt:
    641.61
  • Formula:
    C32H34Cl2N4O4S
  • Solubility:
    Soluble to 100 mM in DMSO
  • Purity:
    >98%
  • Storage:
    Store at +4°C
  • CAS No:
    477575-56-7
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis. All Tocris products are intended for laboratory research use only.
Additional Information
Licensing Caveats:
Sold for research purposes under agreement from Pfizer Inc.
Background References
  1. Efficacy of c-Met inhibitor for advanced prostate cancer.
    Tu et al.
    BMC Cancer, 2010;10:556
  2. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumour activity in vivo.
    Christensen et al.
    Cancer Res., 2003;63:7345
  3. A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts.
    Puri et al.
    Cancer Res., 2007;67:3529
  4. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752.
    Smolen et al.
    Proc.Natl.Acad.Sci.USA, 2006;103:2316
Citations:

The citations listed below are publications that use Tocris products. Selected citations for PHA 665752 include:

22 Citations: Showing 1 - 10
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  1. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing.
    Authors: Valente Et al.
    J Clin Invest 2016;2016:3232859
  2. Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling.
    Authors: Ito Et al.
    Stem Cells Int 2015;308:L1178
  3. The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
    Authors: Saito Et al.
    BMC Cancer 2015;15:82
  4. YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells.
    Authors: Jiang Et al.
    Am J Physiol Lung Cell Mol Physiol 2015;13:280
  5. C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization.
    Authors: Wu Et al.
    Cancer Res 2013;73:5580
  6. EGF receptor activates MET through MAPK to enhance non-small cell lung carcinoma invasion and brain metastasis.
    Authors: Breindel Et al.
    Cancer Res 2013;73:5053
  7. Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition.
    Authors: Katayama Et al.
    Cancer Res 2013;73:3087
  8. A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion.
    Authors: Grugan Et al.
    J Transl Med 2013;14:853
  9. Met receptor acts uniquely for survival and morphogenesis of EGFR-dependent normal mammary epithelial and cancer cells.
    Authors: Accornero Et al.
    PLoS One 2012;7:e44982
  10. Inhibition of hepcidin transcription by growth factors.
    Authors: Goodnough Et al.
    Hepatology 2012;56:291
  11. Passenger deletions generate therapeutic vulnerabilities in cancer.
    Authors: Muller Et al.
    Nature 2012;488:337
  12. Using tandem mass spectrometry in targeted mode to identify activators of class IA PI3K in cancer.
    Authors: Yang Et al.
    Cancer Res 2011;71:5965
  13. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors.
    Authors: Qi Et al.
    Cancer Res 2011;71:1081
  14. Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation.
    Authors: Jiao Et al.
    Mol Cancer 2011;10:125
  15. Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification.
    Authors: Tanizaki Et al.
    Br J Cancer 2011;105:807
  16. Differential roles of STAT3 depending on the mechanism of STAT3 activation in gastric cancer cells.
    Authors: Okamoto Et al.
    Br J Cancer 2011;105:407
  17. Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma.
    Authors: Kongkham Et al.
    Nat Commun 2010;3:336
  18. Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis.
    Authors: Costa Et al.
    FASEB J 2010;24:2680
  19. Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease.
    Authors: Qin Et al.
    Transl Oncol 2010;120:3617
  20. HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion.
    Authors: Hoot Et al.
    J Clin Invest 2010;120:3606
  21. Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells.
    Authors: Kawaguchi Et al.
    Carcinogenesis 2009;30:1097
  22. Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages.
    Authors: Sierra Et al.
    J Exp Med 2008;205:1673
Expand to show all 22 Citations

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