The FGFR (fibroblast growth factor receptor) family, comprising four members, FGFR1, FGFR2, FGFR3 and FGFR4, belongs to the RTKs which serve as high affinity receptors for FGFs controlling cell proliferation, migration, apoptosis and differentiation. BGJ398 is a selective and potent inhibitor of FGFRs with IC50 values of 1 nM for FGFR11-3 and 60 nM for FGFR4, as well as 4.9 nM for FGFR3-K650E mutant (measured by purified recombinant enzymes). Treatment with BGJ398 in cell lysate from HEK293 cells transfected with FGFRs resulted in inhibition on autophosphorylation on specific tyrosine residues of FGFR 1 - 3 with IC50 values below 5 nM. Consistent with the in vitro study, BGJ398 inhibited the proliferation of the FGFR1-, FGFR2-, and FGFR3-dependent BaF3 cells with IC50 values ranged from 0.7 - 52.2 nM depended by different FGFR isoforms. Daily oral treatment with BGJ398 at dose of 10 or 30 mg/kg for 12 consecutive days induced tumor growth inhibition in the orthotopic xenograft bladder cancer model. Similarly, nearly complete tumor stasis was achieved by oral treatment of BGJ398 at dose of 5, 10 and 15 mg/kg in RT112 human bladder cancer xenografted rats[1].
The phosphoproteome of G401 cells was measured in response to Infigratinib, showing significant downregulation of phosphorylation at FRS2 S428 and GAB1 T503, indicating inhibition of the FGFR signaling pathway by the drug.
Mol Syst Biol. 2024 Jan;20(1):28-55.
HCC01-0909 cells
1 µM
24 h
Inhibits FGF/FGFR signaling pathway and its downstream targets, leading to G1 cell cycle arrest
Hepatology. 2019 Mar;69(3):943-958.
ICC13-7
100 nM
24 h
Evaluate the sensitivity of ICC13-7 cells to Infigratinib, showing an IC50 of 12 nM.
Cancer Discov. 2022 May 2;12(5):1378-1395.
ICC21
100 nM
24 h
Evaluate the sensitivity of ICC21 cells to Infigratinib, showing an IC50 of ~250 nM.
Cancer Discov. 2022 May 2;12(5):1378-1395.
ICC10-6
100 nM
24 h
Evaluate the sensitivity of ICC10-6 cells to Infigratinib, showing an IC50 >1000 nM, indicating resistance to Infigratinib.
Cancer Discov. 2022 May 2;12(5):1378-1395.
PDXO67
300 nM
30 min
To confirm FGFR2c activation via endogenous FGF2
NPJ Precis Oncol. 2023 Dec 8;7(1):127.
PDXO67
300 nM
72 h
To evaluate the effect of BGJ398 on proliferation and cell death in PDXO67
NPJ Precis Oncol. 2023 Dec 8;7(1):127.
MPM cell lines
0.1 to 10 µM
72 h
To evaluate the sensitivity of MPM cell lines to Infigratinib, 3 out of 13 cell lines were sensitive to Infigratinib, 4 were resistant, and the remaining 6 showed intermediate sensitivity.
Cells. 2019 Sep 16;8(9):1091.
ICC13-7 cells
100 nM
24 h
To investigate the effect of Infigratinib on glucose metabolism in ICC13-7 cells, the results showed that Infigratinib significantly suppressed glycolytic gene expression and reduced glucose uptake and lactate secretion.
Nat Commun. 2024 May 7;15(1):3805.
ICC21 cells
100 nM
24 h
To investigate the effect of Infigratinib on glucose metabolism in ICC21 cells, the results showed that Infigratinib significantly suppressed glycolytic gene expression and reduced glucose uptake and lactate secretion.
Nat Commun. 2024 May 7;15(1):3805.
Infigratinib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C.B-17 SCID mice
HCC PDX xenograft model
Oral
10, 20, 30 mg/kg
Once daily for 14 days
Infigratinib significantly inhibits tumor growth, reduces tumor burden, and suppresses FGFR signaling pathway and its downstream targets
Hepatology. 2019 Mar;69(3):943-958.
Mice
ICC21 subcutaneous xenograft model
Oral
15 mg/kg
Daily for 21 days
Evaluate the efficacy of Infigratinib combined with Afatinib in the ICC21 subcutaneous xenograft model, showing significant tumor regression with combination therapy.
Cancer Discov. 2022 May 2;12(5):1378-1395.
NSG mice
C666-1 xenograft model
Oral
30 mg/kg
Once daily for 14 days
Evaluate the antitumor effect of Infigratinib on the C666-1 xenograft model, results showed that Infigratinib significantly inhibited tumor growth
Sci Adv. 2022 Apr 8;8(14):eabh2445
Mice
NSG mice
Oral
30 mg/kg
Once daily for 21 days
To evaluate the effect of Infigratinib on tumor growth inhibition and survival in EC PDX models
NPJ Precis Oncol. 2023 Dec 8;7(1):127.
Mice
ICC13-7 xenograft model
Oral
15 mg/kg
Once daily for 10 days
To investigate the effect of Infigratinib on tumor growth in the ICC13-7 xenograft model, the results showed that Infigratinib significantly inhibited tumor growth and reduced glucose uptake.
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