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).
PF-04217903 细胞实验
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.
Hypertension. 2015 Mar;65(3):587-93.
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.
Nat Commun. 2015 May 27;6:7174.
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.
Nat Commun. 2015 May 27;6:7174.
PF-04217903 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
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.
Hypertension. 2015 Mar;65(3):587-93.
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.
Cancer Discov. 2012 Mar;2(3):270-87
Mice
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.
J Clin Invest. 2018 Aug 31;128(9):4086-4097
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.
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