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Submit ReviewPHA 665752
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% (HPLC)
Biological Activity for PHA 665752
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.
Licensing Information
Sold for research purposes under agreement from Pfizer Inc.
Technical Data for PHA 665752
| M. Wt | 641.61 |
| Formula | C32H34Cl2N4O4S |
| Storage | Store at +4°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 477575-56-7 |
| PubChem ID | 10461815 |
| InChI Key | OYONTEXKYJZFHA-SSHUPFPWSA-N |
| Smiles | ClC1=C(CS(C2=CC(/C(C(N4)=O)=C/C3=C(C)C(C(N5CCC[C@@H]5CN6CCCC6)=O)=C(C)N3)=C4C=C2)(=O)=O)C(Cl)=CC=C1 |
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.
Solubility Data for PHA 665752
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 64.16 | 100 |
Preparing Stock Solutions for PHA 665752
The following data is based on the product molecular weight 641.61. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.56 mL | 7.79 mL | 15.59 mL |
| 5 mM | 0.31 mL | 1.56 mL | 3.12 mL |
| 10 mM | 0.16 mL | 0.78 mL | 1.56 mL |
| 50 mM | 0.03 mL | 0.16 mL | 0.31 mL |
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Product Datasheets for PHA 665752
References for PHA 665752
References are publications that support the biological activity of the product.
Christensen et al (2003) A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumour activity in vivo. Cancer Res. 63 7345 PMID: 14612533
Puri et al (2007) A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res. 67 3529 PMID: 17440059
Tu et al (2010) Efficacy of c-Met inhibitor for advanced prostate cancer. BMC Cancer 10 556 PMID: 20946682
Smolen et al (2006) Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc.Natl.Acad.Sci.USA 103 2316
If you know of a relevant reference for PHA 665752, please let us know.
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Keywords: PHA 665752, PHA 665752 supplier, Potent, selective, cMET, inhibitors, inhibits, Hepatocyte, Growth, Factors, Receptors, HGFR, Receptor, Tyrosine, Kinases, RTKs, PHA665752, Pfizer, MET, 2693, Tocris Bioscience
34 Citations for PHA 665752
Citations are publications that use Tocris products. Selected citations for PHA 665752 include:
Gimenez-Xavier et al (2017) Genomic and Molecular Screenings Identify Different Mechanisms for Acquired Resistance to MET Inhibitors in Lung Cancer Cells. Mol Cancer Ther 16 1366 PMID: 28396363
Saito et al (2015) The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma. BMC Cancer 15 82 PMID: 25884729
Grugan et al (2013) A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion. J Transl Med 14 853 PMID: 23792586
Ou et al (2011) Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma. Neoplasia 13 44896 PMID: 21245936
Okamoto et al (2011) Differential roles of STAT3 depending on the mechanism of STAT3 activation in gastric cancer cells. Br J Cancer 105 407 PMID: 21730976
Qi et al (2011) Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors. Cancer Res 71 1081 PMID: 21266357
Yang et al (2011) Using tandem mass spectrometry in targeted mode to identify activators of class IA PI3K in cancer. Cancer Res 71 5965 PMID: 21775521
Jiao et al (2011) Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase coactivation. Mol Cancer 10 125 PMID: 21962244
Tanizaki et al (2011) Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification. Br J Cancer 105 807 PMID: 21847121
Bacco et al (2011) Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 103 645 PMID: 21464397
Choi et al (2019) Hepatocyte Growth Factor Regulates Macrophage Transition to the M2 Phenotype and Promotes Murine Skeletal Muscle Regeneration. Front Physiol 10 914 PMID: 31404148
Holland et al (2015) Effects of AKT inhibition on HGF-mediated erlo. resistance in non-small cell lung cancer cell lines. J Cancer Res Clin Oncol 141 615 PMID: 25323938
D'Alessandro et al (2015) Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling. PLoS Comput Biol 11 e1004192 PMID: 25905717
Katayama et al (2013) Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition. Cancer Res 73 3087 PMID: 23598276
Wu et al (2013) C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization. Cancer Res 73 5580 PMID: 23832667
Breindel et al (2013) EGF receptor activates MET through MAPK to enhance non-small cell lung carcinoma invasion and brain metastasis. Cancer Res 73 5053 PMID: 23794705
Holliday et al (2009) Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression. Breast Cancer Res 11 R3 PMID: 19152687
Blanco et al (2009) A gene-alteration profile of human lung cancer cell lines. Hum Mutat 30 1199 PMID: 19472407
Kawaguchi et al (2009) Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells. Carcinogenesis 30 1097 PMID: 19380521
Rycaj et al (2016) 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. Oncotarget 7 14220 PMID: 26871947
Yen et al (2013) Multipotent Human Mesenchymal Stromal Cells Mediate Expansion of Myeloid-Derived Suppressor Cells via Hepatocyte Growth Factor/c-Met and STAT3. Stem Cell Reports 1 139 PMID: 24052949
Accornero et al (2012) Met receptor acts uniquely for survival and morphogenesis of EGFR-dependent normal mammary epithelial and cancer cells. PLoS One 7 e44982 PMID: 23028720
Goodnough et al (2012) Inhibition of hepcidin transcription by growth factors. Hepatology 56 291 PMID: 22278715
Muller et al (2012) Passenger deletions generate therapeutic vulnerabilities in cancer. Nature 488 337 PMID: 22895339
Cepero et al (2010) MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res 70 7580 PMID: 20841479
Costa et al (2010) Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis. FASEB J 24 2680 PMID: 20354140
Zhou et al (2014) Multipoint targeting of the PI3K/mTOR pathway in mesothelioma. Br J Cancer 110 2479 PMID: 24762959
Hoot et al (2010) HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion. J Clin Invest 120 3606 PMID: 20852387
Qin et al (2010) Failure to ubiquitinate c-Met leads to hyperactivation of mTOR signaling in a mouse model of autosomal dominant polycystic kidney disease. Transl Oncol 120 3617 PMID: 20852388
Kongkham et al (2010) Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma. Nat Commun 3 336 PMID: 21151472
Valente et al (2016) Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing. J Clin Invest 2016 3232859 PMID: 26788066
Jiang et al (2015) YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells. Am J Physiol Lung Cell Mol Physiol 13 280 PMID: 26310485
Ito et al (2015) Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling. Stem Cells Int 308 L1178 PMID: 26033355
Sierra et al (2008) Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages. J Exp Med 205 1673 PMID: 18559453
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