PF-04217903

Catalog No.S1094

PF-04217903 Chemical Structure

Molecular Weight(MW): 372.38

PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.

Size Price Stock Quantity  
In DMSO USD 160 In stock
USD 110 In stock
USD 160 In stock
USD 470 In stock
USD 870 In stock
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3 Customer Reviews

  • (A) p-MET, p-eIF4E, and p-ERK1/2 levels in S462 cells 24 hours after treatment with 1 μM PF04217903 and 750 nM PD901. (B) Change in cell number after treatment with 1 μM PF04217903 (PF903) and/or 750 nM PD901. Graph represents the average log2 of fold change in cell number 72 hours after treatment relative to time 0 (mean ± SD, n = 3).

    J Clin Invest, 2016, 126(6):2181-90. PF-04217903 purchased from Selleck.

    Clonogenicity of LXFA 526L and LXFA 1647L with titration of the MET inhibitor PF-04217903 and combination of PF-04217903 at 0.1 uM with 0.66 uM cetuximab.

    Eur J Cancer 2011 47(8), 1231-43. PF-04217903 purchased from Selleck.

  • Western blot analysis of c-Met, MAPK and Akt. 0-100nM PF04217903 was added.

     

     

    Dr. Zhang of Tianjin Medical University. PF-04217903 purchased from Selleck.

Purity & Quality Control

Choose Selective c-Met Inhibitors

Biological Activity

Description PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.
Targets
c-Met [1]
(A549 cells)
4.8 nM
In vitro

Being more selective than staurosporine or PF-02341066, PF-04217903 displays >1000-fold selectivity for c-Met over a panel of 208 kinases, although more susceptible to oncogenic mutations of c-Met that attenuate potency than PF-02341066. In addition to WT c-Met, PF-04217903 displays similar potency to inhibit the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I with IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, but has no inhibitory activity against c-Met-Y1230C with IC50 of >10 μM. [1] PF-04217903 in combination with sunitinib significantly inhibits endothelial cells, but not the tumor cells B16F1, Tib6, EL4, and LLC [2] PF-04217903 significantly inhibits the clonogenic growth of LXFA 526L and LXFA 1647L with IC50 values of 16 nM, and 13 nM, respectively, yielding an additive effect when in combination with cetuximab. [3] PF-04217903 potently inhibits c-Met-driven processes such as cell growth, motility, invasion, and morphology of a variety of tumor cells. PF-04217903 treatment (2 μM) increased cell death of GTL-16 cells, which involves the downregulation of phosphorylated 4E-BP1, ERK/MAPK associated proteins and PI3K/AKT pathway. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A549 cells NHz1[Y9HfW6ldHnvckBie3OjeR?= M1\wO|EhcA>? NXP3emxVSW62YXfvcol{fCCjY4Tpeol1gSCjdDDjMW1GXCC{ZXPldJRweiCrbjDoeY1idiCDNUS5JINmdGy|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiYYX0c5Bpd3OyaH;yfYxifGmxbjDh[pRmeiBzIHjyJIJ6KEWOSWPBMEBKSzVyPUSgcm0> NISy[GQzOjl{NEezOC=>

... Click to View More Cell Line Experimental Data

In vivo Although unable to inhibit tumor growth in the sunitinib-sensitive B16F1 and Tib6 tumor models, the combination of PF-04217903 and sunitinib significantly inhibits tumor growth in sunitinib-resistant EL4, and LLC tumor models compared with sunitinib or PF-04217903 alone by significantly blocking vascular expansion, indicating a functional role for HGF/c-Met axis in the sunitinib-resistant tumors. [2]

Protocol

Kinase Assay:[1]
+ Expand

Cellular c-Met phosphorylation ELISA:

A549 cells with endogenous human WT c-Met are seeded in 96-well plates in growth medium and cultured overnight. On the second day of the assay, the growth medium is replaced with serum-free medium (with 0.04% BSA). Serial dilutions of PF-04217903 are added to each well, and cells are incubated at 37 °C for 1 hour. Then 40 ng/mL HGF is added to the cells for 20 minutes. The cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells using lysis buffer. Phosphorylation of c-Met is assessed by an ELISA method utilizing capture antibodies specific for c-Met and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are incubated in the presence of protein lysates at 4 °C overnight and washed with 1% Tween 20 in PBS seven times. HRP-PY20 (horseradish peroxidase-conjugated anti-phosphotyrosine) is diluted 1:500 in blocking buffer and added to each plate for 30 minutes. Plates are then washed again, and TMB peroxidase substrate is added to initiate the HRP-dependent colorimetric reaction and the reaction stopped by addition of 0.09 N H2SO4. ELISA end points are the absorbance measured at 450 nm using a spectrophotometer. IC50 value is calculated by concentration-response curve fitting utilizing a Microsoft Excel-based four-parameter analytical met
Cell Research:[2]
+ Expand
  • Cell lines: B16F1, Tib6, EL4, and LLC, HUVECs and C166 cells
  • Concentrations: Dissolved in DMSO, final concentrations ~2 μM
  • Incubation Time: 4 days
  • Method: Cells are treated with different concentrations PF-04217903 for 4 days. Cell proliferation is assessed by counting content of each well using a Coulter counter machine.
    (Only for Reference)
Animal Research:[2]
+ Expand
  • Animal Models: Immunodeficient nude mice (nu/nu) subcutaneously implanted with tumor cell lines B16F1, EL4, LLC, or Tib6
  • Formulation: Dissolved in DMSO, and diluted in saline
  • Dosages: 45 mg/kg
  • Administration: Orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 5 mg/mL (13.42 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 372.38
Formula

C19H16N8O

CAS No. 956905-27-4
Storage powder
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00706355 Terminated Neoplasms Pfizer August 2008 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID