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PF-04217903 phenolsulfonate is a novel, highly potent and ATP-competitive inhibitor of c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met and has antiangiogenic properties.
Targets |
human c-Met (Ki = 4.8 nM)
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ln Vitro |
PF-04217903 phenolsulfonate (0.1-10000 nM; 48-72 hours) inhibits the growth of c-Met–amplified human GTL-16 gastric carcinoma and H1993 NSCLC cells IC50 values of 12 and 30 nM, respectively[1].
PF-04217903 phenolsulfonate (1.5-3333 nM; 48 hours) causes GTL-16 cells to undergo apoptosis (IC50=31 nM)[1]. PF-04217903 phenolsulfonate also has IC50 values comparable to those for inhibiting c-Met phosphorylation in these cell lines (IC50=7-12.5 nM), which means it inhibits HGF-mediated cell migration and Matrigel invasion in a number of c-Met-overexpressing tumor cell lines, including human NCI-H441 lung carcinoma and HT29 colon carcinoma[1]. PF-04217903 phenolsulfonate has an IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, showing comparable potency to inhibit the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I. A c-Met-Y1230C IC50 of >10 μM indicates that PF-04217903 phenolsulfonate exhibits no inhibitory activity[3]. |
ln Vivo |
Phenolsulfonate (PF-04217903; p.o., 1–30 mg/kg; daily for 16 days) inhibits tumor growth in a dose-dependent manner, and this effect is correlated with the tumors' decreased c-Met phosphorylation[1].
PF-04217903 phenolsulfonate (5-50 mg/kg, p.o.; once daily for 3 days) induces apoptosis (cleaved caspase-3) in U87MG xenograft tumors at all dose levels while dose-dependently inhibiting phosphorylation of c-Met, Gab-1, Erk1/2, and AKT. In both the GTL-16 and U87MG models, PF-04217903 phenolsulfonate significantly and dose-dependently lowers human IL-8 levels, and in the GTL-16 model, it lowers human VEGFA levels. In U87MG xenograft tumors, PF-04217903 phenolsulfonate significantly increases phospho-PDGFRβ levels[1]. |
Cell Assay |
Cell Line: GTL-16, H1993 cells
Concentration: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 48-72 hours Result: Inhibited proliferation of c-Met–amplified human GTL-16 gastric carcinoma and H1993 NSCLC cells with IC50 values of 12 and 30 nM, respectively. |
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 |
C19H16N8O
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Molecular Weight |
372.383341789246
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Exact Mass |
546.14
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Elemental Analysis |
C, 54.94; H, 4.06; N, 20.50; O, 14.64; S, 5.87
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CAS # |
1159490-85-3
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Related CAS # |
PF-04217903;956905-27-4;PF-04217903 mesylate;956906-93-7
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Appearance |
Solid powder
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SMILES |
C1=CC2=C(C=CC(=C2)CN3C4=NC(=CN=C4N=N3)C5=CN(N=C5)CCO)N=C1
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InChi Key |
PDMUGYOXRHVNMO-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C19H16N8O/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/h1-5,8-10,12,28H,6-7,11H2
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Chemical Name |
2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol
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Synonyms |
PF-04217903 phenolsulfonate; PF 04217903 phenolsulfonate; PF04217903 phenolsulfonate
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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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6854 mL | 13.4271 mL | 26.8543 mL | |
5 mM | 0.5371 mL | 2.6854 mL | 5.3709 mL | |
10 mM | 0.2685 mL | 1.3427 mL | 2.6854 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.
Effect of PF-04217903 on Met phosphorylation in GTL-16, NCI-H1993, and HT29 cells (A); cell proliferation in GTL-16, NCI-H1993, U87MG, SW620, and HT29 cells (B); GTL-16 cell apoptosis (C); and NC1-H441 cell Matrigel invasion in vitro (D). A, the cells were seeded in the 96-well plates and were treated with designated concentrations of PF-04217903 for 1 hour. Mol Cancer Ther . 2012 Apr;11(4):1036-47. td> |
Inhibition of c-Met phosphorylation (A, D, E), tumor growth (B–D), c-Met downstream signal transduction (F), tumor cell proliferation (G), and induction of apoptosis (H) by PF-04217903 in GTL-16 xenograft model. Mol Cancer Ther . 2012 Apr;11(4):1036-47. td> |
Effect of PF-04217903 on tumor MVD (A) or secretion of proangiogenic factors (B and C) in tumor xenografts in vivo. Mol Cancer Ther . 2012 Apr;11(4):1036-47. td> |