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PHA-665752

Cat. No. M1899
PHA-665752 Structure
Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
10mg USD 90 In stock
50mg USD 360 In stock
100mg USD 640 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

PHA-665752 is a small-molecule inhibitor of c-Met, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). PHA665752 inhibited specific phosphorylation of TPR-MET as well as phosphorylation of downstream targets of the mammalian target of rapamycin pathway. Short-term treatment with PHA-665752 decreased the numbers of premalignant lung lesions and induced apoptosis in tumor cells and vascular endothelial cells within lesions. In cell culture, PHA-665752 induced apoptosis of a lung adenocarcinoma cell line derived from Kras(LA1) mice (LKR-13) and a murine lung endothelial cell line (MEC). PHA665752 was shown to inhibit cMet/HGF/SF signaling in vitro, suggesting c-Met inhibitors may have efficacy for blocking local progression and/or metastatic spread of c-Met-positive NBL in vivo.

Protocol
Cell Experiment
Cell lines S114, GTL-16, NCI-H441, or BxPC-3 cells
Preparation method Cell Proliferation Assays. S114, GTL-16, NCI-H441, or BxPC-3 cells were seeded in 96-well plates at 9000 cells/well in medium with 10% FBS. After incubation for 48 h in low serum (0.5% FBS, S114; 0.1% FBS, GTL-16, NCI-H441, and BxPC-3), cells were treated with different concentrations of PHA-665752 for 18 h at 37°C. HGF (50 ng/ml) was added for 18 h before BrdUrd for studies involving GTL-16, H441, and BxPC-3. After incubation with BrdUrd labeling reagent for 1 h (Sigma Biochemicals, St. Louis, MO), cells were fixed and BrdUrd incorporation into newly synthesized DNA was assessed using anti-BrdUrd peroxidase-conjugated antibody followed by colorimetric determination at 630 nm.
Concentrations 0~1.25µM
Incubation time 18h
Animal Experiment
Animal models athymic mice bearing S114 or GTL-16 tumor xenografts
Formulation L-lactate (pH 4.8) and 10% polyethylene glycol
Dosages 7.5, 15, 30 mg/kg/day
Administration i.v. bolus via tail vein injection
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 641.61
Formula C32H34Cl2N4O4S
CAS Number 477575-56-7
Purity >98%
Solubility DMSO 100 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Biochem Biophys Res Commun (2014). Figure 2.PHA-665752
Method MTT assay
Cell Lines CNE-1 and HONE-1 cells
Concentrations 2 μM
Incubation Time 72 h
Results Further experiments showed that PHA-665752 inhibited cell proliferation in a dose-dependent manner in the CNE-1 and HONE-1 cells
Rating
References

PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells.
Crosswell HE, et al. BMC Cancer. 2009 Nov 25;9:411. PMID: 19939254.

A selective small molecule inhibitor of c-Met, PHA-665752, reverses lung premalignancy induced by mutant K-ras.
Yang Y, et al. Mol Cancer Ther. 2008 Apr;7(4):952-60. PMID: 18413809.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PHA-665752 supplier, c-Met, inhibitors

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