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Purity: ≥98%
PF-04217903 mesylate, the methanesulfonate salt of PF-04217903, is a novel, potent, orally bioavailabe, selective, and ATP-competitive small-molecule tyrosine kinase inhibitor of c-Met with IC50 of 4.8 nM in A549 cell line and with anticancer activity, it is susceptible to oncogenic mutations (with no activity to Y1230C mutant). By specifically binding to and inhibiting c-Met, PF-04217903 disrupts the c-Met signaling pathway, potentially impairing the growth, migration, and invasion of tumor cells as well as causing tumor cells that express c-Met to die.
| Targets |
human c-Met (Ki = 4.8 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In 96-well plates, A549 cells expressing endogenous human WT c-Met are plated in growth medium and allowed to grow for the entire night. The growth medium is switched out for serum-free medium (containing 0.04% BSA) on the second day of the experiment. Each well receives serial dilutions of PF-04217903, and the cells are incubated for an hour at 37 °C. The cells are then treated with 40 ng/mL of HGF for 20 minutes. After giving the cells one wash in HBSS supplemented with 1 mM Na3VO4, lysis buffer is used to extract the protein from the cells. An ELISA technique that uses capture antibodies specific to c-Met and a detection antibody specific to phosphorylated tyrosine residues is used to measure the phosphorylation of c-Met. Protein lysates are added to antibody-coated plates, which are then incubated at 4 °C for an entire night before being seven times cleaned with 1% Tween 20 in PBS. Each plate is treated with 1:500 diluted horseradish peroxidase-conjugated anti-phosphotyrosine (HRP-PY20) for 30 minutes. After another round of washing the plates, the HRP-dependent colorimetric reaction is started with the addition of TMB peroxidase substrate, and it is halted with the addition of 0.09 N H2SO4. Using a spectrophotometer, the absorbance at 450 nm is used to determine the ELISA end points. By fitting a concentration-response curve with a four-parameter analytical method based on Microsoft Excel, the IC50 value is determined.
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| Cell Assay |
For four days, cells (B16F1, Tib6, EL4, LLC, HUVECs, and C166 cells) are treated with varying concentrations of PF-04217903. Using a Coulter counter machine, the content of each well is counted to determine the amount of cell proliferation.
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| Animal Protocol |
Female nu/nu mice GTL-16 xenograft model
1, 3, 10, 30 mg/kg Oral; daily for 16 days |
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| References |
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| Molecular Formula |
C20H20N8O4S
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| Molecular Weight |
468.492
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| Exact Mass |
468.13282232
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| Elemental Analysis |
C, 51.28; H, 4.30; N, 23.92; O, 13.66; S, 6.84
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| CAS # |
956906-93-7
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| Related CAS # |
PF-04217903;956905-27-4;PF-04217903 phenolsulfonate;1159490-85-3
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| Appearance |
Solid powder
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| SMILES |
CS(=O)(=O)O.C1=CC2=C(C=CC(=C2)CN3C4=NC(=CN=C4N=N3)C5=CN(N=C5)CCO)N=C1
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| InChi Key |
HBEMHKVWZJTVOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H16N8O.CH4O3S/c28-7-6-26-12-15(9-22-26)17-10-21-18-19(23-17)27(25-24-18)11-13-3-4-16-14(8-13)2-1-5-20-16;1-5(2,3)4/h1-5,8-10,12,28H,6-7,11H2;1H3,(H,2,3,4)
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| Chemical Name |
methanesulfonic acid;2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol
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| Synonyms |
PF04217903 mesylate; PF 04217903; PF-04217903; PF4217903 mesylate; PF-4217903; PF 4217903 mesylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1345 mL | 10.6726 mL | 21.3452 mL | |
| 5 mM | 0.4269 mL | 2.1345 mL | 4.2690 mL | |
| 10 mM | 0.2135 mL | 1.0673 mL | 2.1345 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Endothelial cells, but not tumor cells, are mainly targeted by HGF/c-Met axis.Cancer Res.2010Dec 15;70(24):10090-100. |
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