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PHA 665752

Catalog #: 2693
34 Citations Datasheet / COA / SDS
Catalog # Availability Size / Price Qty
2693/10
2693/50
PHA 665752 | CAS No. 477575-56-7 | MET Inhibitors
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Description: Potent and selective MET inhibitor

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

Purity: ≥98%

Product Details
Citations (34)
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Biological Activity Technical Data Additional Information Background Product Datasheets Calculators

Biological Activity

PHA 665752 is a 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.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Additional Information

Licensing Caveats:
Sold for research purposes under agreement from Pfizer Inc.

Background References

  1. Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain
    E Paldy, M Simonetti, T Worzfeld, KK Bali, L Vicuña, S Offermanns, R Kuner
    Nat Commun, 2017;8(1):176.
  2. MET inhibition overcomes radiation resistance of glioblastoma stem-like cells

    EMBO Mol Med, 2016;8(5):550-68.
  3. RhoA/phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein kinase signaling after growth arrest-specific protein 6/mer receptor tyrosine kinase engagement promotes epithelial cell growth and wound repair via upregulation of hepatocyte growth factor in macrophages.
    Lee Y, Park H, Woo S, Park E, Kang J
    J Pharmacol Exp Ther, 2014;350(3):563-77.
  4. Met receptor acts uniquely for survival and morphogenesis of EGFR-dependent normal mammary epithelial and cancer cells.
    Accornero, Paolo, Miretti, Silvia, Bersani, Francesc, Quaglino, Elena, Martignani, Eugenio, Baratta, Mario
    PLoS ONE, 2012;7(9):e44982.
  5. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET.
    Basilico C, Pennacchietti S, Vigna E, Chiriaco C, Arena S, Bardelli A, Valdembri D, Serini G, Michieli P
    Clin Cancer Res, 2013;19(9):2381-92.
  6. Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-beta.
    Wiener Z, Band A, Kallio P, Hogstrom J, Hyvonen V, Kaijalainen S, Ritvos O, Haglund C, Kruuna O, Robine S, Louvard D, Ben-Neriah Y, Alitalo K
    Proc Natl Acad Sci U S A, 2014;111(21):E2229-36.
  7. The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
    Saito S, Morishima K, Ui T, Hoshino H, Matsubara D, Ishikawa S, Aburatani H, Fukayama M, Hosoya Y, Sata N, Lefor A, Yasuda Y, Niki T
    BMC Cancer, 2015;15(0):82.
  8. Hedgehog pathway signaling regulates human colon carcinoma HT-29 epithelial cell line apoptosis and cytokine secretion.
    Yoshimoto A, Bernardazzi C, Carneiro A, Elia C, Martinusso C, Ventura G, Castelo-Branco M, de Souza H
    PLoS ONE, 2012;7(9):e45332.
  9. 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
  10. 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
  11. Efficacy of c-Met inhibitor for advanced prostate cancer.
    Tu et al.
    BMC Cancer, 2010;10:556
  12. 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

Product Datasheets

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Citations for PHA 665752

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

34 Citations: Showing 1 - 10

  1. Hepatocyte Growth Factor Regulates Macrophage Transition to the M2 Phenotype and Promotes Murine Skeletal Muscle Regeneration.
    Authors: Choi Et al.
    Front Physiol  2019;10:914
  2. Genomic and Molecular Screenings Identify Different Mechanisms for Acquired Resistance to MET Inhibitors in Lung Cancer Cells.
    Authors: Gimenez-Xavier Et al.
    Mol Cancer Ther  2017;16:1366
  3. Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-/lo castration-resistant cells.
    Authors: Rycaj Et al.
    Oncotarget  2016;7:14220
  4. 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
  5. 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
  6. 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
  7. Effects of AKT inhibition on HGF-mediated erlo. resistance in non-small cell lung cancer cell lines.
    Authors: Holland Et al.
    J Cancer Res Clin Oncol  2015;141:615
  8. 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
  9. Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling.
    Authors: D'Alessandro Et al.
    PLoS Comput Biol  2015;11:e1004192
  10. Multipoint targeting of the PI3K/mTOR pathway in mesothelioma.
    Authors: Zhou Et al.
    Br J Cancer  2014;110:2479
  11. C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization.
    Authors: Wu Et al.
    Cancer Res  2013;73:5580
  12. 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
  13. Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition.
    Authors: Katayama Et al.
    Cancer Res  2013;73:3087
  14. Multipotent Human Mesenchymal Stromal Cells Mediate Expansion of Myeloid-Derived Suppressor Cells via Hepatocyte Growth Factor/c-Met and STAT3.
    Authors: Yen Et al.
    Stem Cell Reports  2013;1:139
  15. 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
  16. 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
  17. Inhibition of hepcidin transcription by growth factors.
    Authors: Goodnough Et al.
    Hepatology  2012;56:291
  18. Passenger deletions generate therapeutic vulnerabilities in cancer.
    Authors: Muller Et al.
    Nature  2012;488:337
  19. 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
  20. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors.
    Authors: Qi Et al.
    Cancer Res  2011;71:1081
  21. Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma.
    Authors: Ou Et al.
    Neoplasia  2011;13:44896
  22. Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation.
    Authors: Jiao Et al.
    Mol Cancer  2011;10:125
  23. 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
  24. 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
  25. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer.
    Authors: Bacco Et al.
    J Natl Cancer Inst  2011;103:645
  26. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors.
    Authors: Cepero Et al.
    Cancer Res  2010;70:7580
  27. Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma.
    Authors: Kongkham Et al.
    Nat Commun  2010;3:336
  28. Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis.
    Authors: Costa Et al.
    FASEB J  2010;24:2680
  29. 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
  30. HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion.
    Authors: Hoot Et al.
    J Clin Invest  2010;120:3606
  31. A gene-alteration profile of human lung cancer cell lines.
    Authors: Blanco Et al.
    Hum Mutat  2009;30:1199
  32. Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells.
    Authors: Kawaguchi Et al.
    Carcinogenesis  2009;30:1097
  33. Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression.
    Authors: Holliday Et al.
    Breast Cancer Res  2009;11:R3
  34. Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages.
    Authors: Sierra Et al.
    J Exp Med  2008;205:1673

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