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Chemical Structure| 956905-27-4 Chemical Structure| 956905-27-4

Structure of PF-04217903
CAS No.: 956905-27-4

Chemical Structure| 956905-27-4

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

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Product Details of PF-04217903

CAS No. :956905-27-4
Formula : C19H16N8O
M.W : 372.38
SMILES Code : OCCN1N=CC(C2=CN=C3C(N(CC4=CC=C5N=CC=CC5=C4)N=N3)=N2)=C1
MDL No. :MFCD12407410
InChI Key :PDMUGYOXRHVNMO-UHFFFAOYSA-N
Pubchem ID :17754438

Safety of PF-04217903

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Related Pathways of PF-04217903

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human aortic endothelial cells (HAECs) 6 μg/ml 1 hour To study the effect of HGF on LPS-induced inflammation, results showed that HGF reduced the expression of VCAM-1 and E-Selectin, while the c-Met antagonist PF-04217903 abolished the protective effect of HGF. PMC4326566
293FT cells 100 nM 4 hours To evaluate the inhibitory effect of PF-04217903 on MET fusion kinases, results showed that PF-04217903 significantly reduced p-MET and downstream signaling pathway activity. PMC4446791
Mouse melanocytes 100 nM 4 hours To evaluate the inhibitory effect of PF-04217903 on MET fusion kinases, results showed that PF-04217903 significantly reduced p-MET and downstream signaling pathway activity. PMC4446791

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice RIP-Tag2 transgenic mice Oral gavage 30 mg/kg Once daily for 3 weeks To investigate the inhibitory effect of PF-04217903 on tumor invasion and metastasis, results showed that PF-04217903 significantly reduced tumor invasiveness and liver metastasis. PMC3354652
C57BL/6J mice RIP-Tag2 transgenic mice Oral 30mg/kg Once daily for 3 weeks PF-04217903 significantly reduced metastasis to local lymph nodes, indicating that c-Met signaling plays an important role in tumor cell spread to lymph nodes. PMC3686901
mouse Met-amplified ATC cell allograft model Oral 30 mg/kg or 45 mg/kg once daily for 15 days To evaluate the antitumor effects of PF-04217903 in Met-amplified ATC allograft models, results showed that PF-04217903 significantly inhibited the growth of Met-amplified tumors but was ineffective in Met-diploid allografts. PMC6118575
C57BL/6 mice Intracranial aneurysm model Oral gavage 10 mg/kg/day Once daily for 21 days To study the effect of the c-Met antagonist PF-04217903 on the formation and rupture of intracranial aneurysms, results showed that PF-04217903 significantly increased the prevalence of subarachnoid hemorrhage and decreased survival in mice. PMC4326566

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00706355 Neoplasms PHASE1 TERMINATED 2025-06-11 Pfizer Investigational Site, A... More >>urora, Colorado, 80045, United States|Pfizer Investigational Site, Chicago, Illinois, 60637, United States|Pfizer Investigational Site, Boston, Massachusetts, 02114, United States|Pfizer Investigational Site, Boston, Massachusetts, 02115, United States|Pfizer Investigational Site, Boston, Massachusetts, 02215, United States|Pfizer Investigational Site, Detroit, Michigan, 48201, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.43mL

2.69mL

1.34mL

26.85mL

5.37mL

2.69mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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