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PF-04217903

Cat. No. M1766

PF-04217903 Structure

Synonym: PF-4217903

Size Price Availability Quantity
10mg USD 120 In stock
50mg USD 350 In stock
100mg USD 600 In stock
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Quality Control
Biological Activity

PF-04217903 (PF-4217903) is a novel ATP-competitive small molecule inhibitor of c-Met kinases with the IC50 values from 3.1 nM to 142 nM. PF-04217903 (PF-4217903) demonstrated >1000 fold selectivity for c-Met compared with >150 kinases, making it one of the most selective c-Met inhibitors described to date. PF-04217903 (PF-4217903) inhibited tumor cell proliferation, survival, migration/invasion in MET amplified cell lines in vitro, and demonstrated marked antitumor activity in tumor models harboring either MET gene amplification or a HGF/c-Met autocrine loop at well-tolerated dose levels in vivo.

Protocol
Cell Experiment
Cell lines B16F1, Tib6, EL4, and LLC, and endothelial cells, HUVECs and C166
Preparation method Cell lines, including B16F1, Tib6, EL4, and LLC, and endothelial cells, HUVECs and C166, were seeded at 104 cells in each well of 24-well tissue culture–treated plates. Cells were grown in the standard media as described earlier. Cells were treated with different concentrations (2, 0.2, and 0.02 μmol/L) of sunitinib, PF-04217903, and combination of both compounds for 4 days. Efficacy of the compounds was measured by counting cells in a Coulter counter machine (BD Biosciences). Similar approach was applied to evaluate the role of HGF or VEGF on cell proliferation, using 3 different concentrations (10, 100, and 200 ng/mL) of each ligand.
Concentrations 2, 0.2, and 0.02 μmol/L
Incubation time 4 days
Animal Experiment
Animal models B16F10 tumour-bearing mice
Formulation 0.5% methylcellulose in saline
Dosages 40mg/kg PF-04217903
Administration oral
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 372.38
Formula C19H16N8O
CAS Number 956905-27-4
Purity >99%
Solubility DMSO ≥75 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Nature (2015). Figure 3. PF-04217903 and INCB28060 (AbMole Bioscience)
Method mice treatment in vivo and histological evaluation
Cell Lines B16F10 cells
Concentrations 40mg/kg PF-04217903 and 50mg/kg INCB28060
Incubation Time 2 weeks
Results Systemic treatment of WT mice carrying B16F10 melanomas (which are dependent on MET14) with three different MET tyrosine-kinase inhibitors (PF-04217903, INCB28060 and JNJ-38877605), strongly reduced TAN recruitment .
Rating
Source Nature (2015). Figure 2. PF-04217903 and INCB28060 (AbMole Bioscience)
Method mice treatment in vivo and histological evaluation
Cell Lines B16F10 cells
Concentrations 40mg/kg PF-04217903
Incubation Time 2 weeks
Results "Systemic administration of PF-04217903 decreased the weight and volume of B16F10 melanomas by 36% and 54%, respectively. Instead, MET knockdown in cancer cells only, led to 58% and 75% inhibition of tumour growth and volume.TAN inhibition by PF-04217903 was comparable in both Met-silenced and scrambled B16F10 melanomas."
Rating
Product Citations
References

Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer.
Cui JJ, et al. J Med Chem. 2012 Sep 27;55(18):8091-109. PMID: 22924734.

A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells though MAPK activation.
Lee NV, et al. PLoS One. 2012;7(6):e39653. PMID: 22745804.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PF-04217903, PF-4217903 supplier, c-Met, inhibitors

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