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• 产品描述： Infigratinib (BGJ398) is an orally bioavailable pan FGFR inhibitor (IC50: 0.9/1.4/1 nM for FGFR1/2/3), >40-fold selective for FGFR versus FGFR4 and VEGFR2.

• 靶点： Apoptosis;FGFR;Apoptosis; FGFR

• 体内研究：
  When tested in this orthotopic xenograft bladder cancer model, NVP-BGJ398 (10 and 30 mg/kg) induced tumor growth inhibition and stasis after oral administration for 12 consecutive days. The monophosphate salt of 1h was orally administered to juvenile, immunocompromised, female Rowett rats for 20 consecutive days (20 administrations) at the doses of 5, 10, and 15 mg/kg/qd (free base equivalents). Nearly complete tumor stasis was achieved at the lowest dose while no overt toxicity was observed. The doses of 10 and 15 mg/kg provided tumor regression which was accompanied by a dose-dependent decrease of body weight. NVP-BGJ398 (30 mg/kg, p.o.) significantly delayed the growth of FGFR2-mutated endometrial cancer xenograft tumors. NVP-BGJ398 had no in vivo inhibitory effects in the long-term study using the FGFR2 wild-type endometrial cancer cell line SNGM

• 细胞实验： Murine BaF3 cell lines, whose proliferation and survival has been rendered IL-3-independent by stable transduction with tyrosine kinases activated either by mutation or fusion with a dimerizing partner, were cultured in RPMI-1640 media supplemented with 10% FBS, 4.5 g/L glucose, 1.5 g/L sodium bicarbonate, and Pen/Strep. Cells were passaged twice weekly. Compound-mediated inhibition of BaF3 cell proliferation and viability was assessed using a Luciferase bioluminescent assay. Exponentially growing BaF3 or BaF3 Tel-TK cells were seeded into 384-well plates (4250 cells/well) at 50 μL/well using a μFill liquid dispenser in fresh medium. NVP-BGJ398 was serially diluted in DMSO and arrayed in a polypropylene 384-well plate. Then 50 nL of compound was transferred into the plates containing the cells by using the pintool transfer device, and the plates incubated at 37 ℃ (5% CO2) for 48 h. Then 25 μL of Bright-Glo were added, and luminescence was quantified using an Analyst-GT. Custom curve-fitting software was used

• 动物实验： We used FGFR2-mutated MFE296, AN3CA, and FGFR2 wild-type SNGM and HEC1A endometrial cancer cells, which spontaneously formed xenografts in athymic mice for our in vivo studies. Mice were maintained and handled under aseptic conditions, and animals were allowed access to food and water ad libitum. Female athymic mice (20.0–30.0 g) aged 4 to 6 weeks from an outbred strain (CD1 nu/nu) were injected subcutaneously (2 × 10^7 cells per mouse) in the flank. AN3CA cells were suspended in Matrigel and DMEM (volume 1:1). A period of 7 days elapsed to allow the formation of tumor nodules (mean xenograft volume = 105 ± 5.6 mm^3). Mice were then stratified into treatment groups with one tumor per mouse on the basis of their weight and tumor volume at the start of the experiment, such that the starting weight and tumor volume in each group were uniform. Mice (10/group) were treated via oral gavage of (i) vehicle control (5 mmol/L sodium citrate and 1 μL 6N HCL/mL), (ii) NVP-BGJ398 30 mg/kg (6 mg in 0.5 mL PEG300 and 0.5 mL

• 参考文献：
  1.Guagnano V, et al. Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem. 2011 Oct 27;54(20):7066-83. 2.Konecny GE, et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Mol Cancer Ther. 2013 May;12(5):632-42. 3.Guagnano V, et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov. 2012 Dec;2(12):1118-33. 4.Lin H, Lu P, Zhou M, et al. Purification of recombinant human fibroblast growth factor 13 in E. coli and its molecular mechanism of mitogenesis[J]. Applied microbiology and biotechnology. 2019: 1-11. 5.Pu X, Ye Q, Cai J, et al. Typing FGFR2 translocation determines the response to targeted therapy of intrahepatic cholangiocarcinomas[J]. Cell death & disease. 2021, 12(3): 1-14.

• 溶解性： DMSO:48.2  mM

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.784 ml	8.921 ml	17.842 ml
  5 mM	0.357 ml	1.784 ml	3.568 ml
  10 mM	0.178 ml	0.892 ml	1.784 ml
  50 mM	0.036 ml	0.178 ml	0.357 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *