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网站主页 化工产品目录 生物化工 抑制剂 血管生成(Angiogenesis) FGFR 抑制剂 FGFR抑制剂(NVP-BGJ398) 化合物 Infigratinib
  • 化合物 Infigratinib|T1975|TargetMol

化合物 Infigratinib|T1975|TargetMol

Infigratinib
872511-34-7
185 1mg 起订
413 5mg 起订
496 10mg 起订
上海 更新日期:2024-12-02

TargetMol中国(陶术生物)

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产品详情:

中文名称:
化合物 Infigratinib
英文名称:
Infigratinib
CAS号:
872511-34-7
品牌:
TargetMol
产地:
美国
保存条件:
Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
纯度规格:
98.46%
产品类别:
抑制剂
货号:
T1975

Product Introduction

Bioactivity

名称Infigratinib
描述Infigratinib (NVP-BGJ398) (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.
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 to produce a logistic fit of percent cell viability as a function of the logarithm of inhibitor concentration. The IC50 value was determined as the concentration of compound needed to reduce cell viability to 50% of a DMSO control [1].
激酶实验The enzymatic kinase activity is assessed by measuring the phosphorylation of a synthetic substrate by the purified GST-fusion FGFR3-K650E kinase domain, in the presence of radiolabeled ATP. Enzyme activities are measured by mixing 10 μL of a 3-fold concentrated NVP-BGJ398 solution or control with 10 μL of the corresponding substrate mixture (peptidic substrate, ATP and [γ33P]ATP). The reactions are initiated by addition of 10 μL of a 3-fold concentrated solution of the enzyme in assay buffer. The final concentrations of the assay components are as following: 10 ng of GST-FGFR3-K650E, 20 mM Tris-HCl, pH 7.5, 3 mM MnCl2, 3 mM MgCl2, 1 mM DTT, 250 μg/mL PEG 20000, 2 μg/mL poly(EY) 4:1, 1% DMSO and 0.5 μM ATP (γ-[33P]-ATP 0.1 μCi). The assay is carried out according to the filter binding (FB) method in 96-well plates at room temperature for 10 min in a final volume of 30 μL including the components as indicated above. The enzymatic reactions are stopped by the addition of 20 μL of 125 mM EDTA, and the incorporation of 33P into the polypeptidic substrates is quantified as following: 30 μL of the stopped reaction mixture are transferred onto Immobilon-PVDF membranes previously soaked for 5 min with methanol, rinsed with water, soaked for 5 min with 0.5% H3PO4, and mounted on vacuum manifold with disconnected vacuum source. After spotting, vacuum is connected, and each well rinsed with 0.5% H3PO4 (200 μL). Free membranes are removed and washed four times on a shaker with 1% H3PO4 and once with ethanol. Membranes are dried and overlaid with addition of 10 μL/well of scintillation fluid. The plates are eventually sealed and counted in a microplate scintillation counter. IC50 values are calculated by linear regression analysis of the percentage inhibition of NVP-BGJ398 [1].
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 acetic acid/acetate buffer, pH 4.68), (iii) dovitinib 30 mg/kg (1 mg in 1 mL of 5 mmol/L sodium citrate and 1 μL 6N HCL/mL), and (iv) dovitinib 50 mg/kg (1 mg in 1 mL of 5 mmol/L sodium citrate and 1 μL 6N HCL/mL). Treatment was continuous on a daily basis. Tumors were monitored by serial micrometer measurements made by a single observer with tumor volumes calculated length × width × depth. Differences in xenograft volume between groups were analyzed by Student t test of the tumor volume data [3].
体外活性Infigratinib (NVP-BGJ398) inhibited FGFR1/2/3 (IC50: 1 nM), FGFR3-K650E (IC50: 4.9 nM), and FGFR4 (IC50: 60 nM). NVP-BGJ398 inhibited the proliferation of the FGFR1-, FGFR2-, and FGFR3-dependent BaF3 cells with IC50 values which were in the low nanomolar range and comparable to those observed for the inhibition of the receptors kinase activity in the enzymatic assay [1]. Among the 35 cell lines selected from the high-throughput assays, 28 were confirmed as sensitive to NVP-BGJ398 (IC50s: 0.001 to 500 nmol/L). Collectively, among the 541 (517 + 24) cell lines from the CCLE subjected to viability testing, 5.9% were found to be sensitive to NVP-BGJ398 [2]. Cell lines with activating FGFR2 mutations (S252W, N550K) were more sensitive to NVP-BGJ398 when compared with their FGFR2 wild-type counterparts. NVP-BGJ398 was potent at inhibiting cell growth of FGFR2-mutant endometrial cancer cells [3].
体内活性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 [1]. 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 [2].
存储条件Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
溶解度DMSO : 5.61 mg/mL (10 mM), Sonication is recommended.
关键字Apoptosis | Fibroblast growth factor receptor | BGJ 398 | inhibit | Infigratinib | Inhibitor | NVP-BGJ-398 | FGFR | NVP-BGJ 398 | BGJ398
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NVP-BGJ398|||BGJ-398|TargetMol

公司简介

上海陶术生物科技有限公司为美国Target Molecule Corp. ( Target Mol ) 在上海建立的全资子公司。我们与美国波士顿、德国慕尼黑的同事一起,为北美、欧洲和亚洲从事药物研发和生物学研究的科学家提供优质的产品和专业的服务。公司下设筛选事业部,化学事业部,生物事业部和新材料部。 从虚拟筛选到实体化合物分子供应;从商业化产品销售到个性化定制合成;从对明确靶点的分子筛选到对明确分子的多靶点筛选,从高通量筛选到化学结构优化,我们都可以满足您的科研用品及技术服务的需求。 经过在中国市场五年的精心耕耘,我们已成为筛选化合物领域优秀的供应商,为超过五百家学校和各类企业提供了品质卓越的小分子化合物和药物筛

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