Infigratinib (BGJ398)

製品コードS2183 バッチS218307

印刷

化学情報

Chemical Structure Synonyms NVP-BGJ398 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H31Cl2N7O3
分子量 560.48 CAS No. 872511-34-7
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 27 mg/mL (48.17 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Infigratinib (BGJ398) is a potent and selective FGFR inhibitor for FGFR1/2/3 with IC50 of 0.9 nM/1.4 nM/1 nM in cell-free assays, >40-fold selective for FGFR versus FGFR4 and VEGFR2, and little activity to Abl, Fyn, Kit, Lck, Lyn and Yes. Phase 2.
in vitro Infigratinib (BGJ398) also prevents VEGFR2 with low potency. The IC50 of this compound for inhibiting VEGFR2 is 0.18 μM. It suppresses other kinases including ABL, FYN, KIT, LCK, LYN and YES with IC50 of 2.3 μM, 1.9 μM, 0.75 μM, 2.5 μM, 0.3 μM and 1.1 μM, respectively. At the cellular level, it inhibits the proliferation of the FGFR1-, FGFR2-Q, and FGFR3-dependent BaF3 cells with IC50 of 2.9 μM, 2.0 μM and 2 μM, respectively. It interferes with autophosphorylation on specific tyrosine residues including FGFR-WT, FGFR2-WT, FGFR3-K650E, FGFR3-S249C and FGFR4-WT with IC50 of 4.6 nM, 4.9 nM, 5 nM, 5 nM and 168 nM, respectively. It suppresses proliferation of the cancer cells with wild-type (WT) FGFR3 overexpression such as RT112, RT4, SW780 and JMSU1 with IC50 of 5 nM, 30 nM, 32 nM and 15 nM, respectively. [1]
in vivo In this orthotopic xenograft bladder cancer model, Infigratinib (BGJ398) induces tumor growth inhibition and stasis after oral administration for 12 consecutive days at the doses of 10 and 30 mg/kg, respectively. Interestingly, the animals that received it exhibit either no body weight loss (10 mg/kg) or 10% body weight gain (30 mg/kg), a further indication of efficacy. RT112 tumor-bearing and female Rowett rats receive a single oral administration of the monophosphate salt of this compound at the doses of 4.25 and 8.51 mg/kg. It significantly decreases the levels of pFRS2 and pMAPK in a dose-dependent manner and inhibits significantly bFGF-stimulated angiogenesis in a dose-dependent manner. However, it does not impair VEGF-induced blood vessel formation. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Radiometric kinase assay
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 solution of Infigratinib (BGJ398) 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 minutes in a final volume of 30 μL including this compound. 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 minutes 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 ished four times on a shaker with 1% H3PO4 and once with ethanol. Membranes are dried and overlaid with addition of 10 μL/well of a 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 it.
細胞アッセイ 細胞株 Murine BaF3 cell lines
濃度 0 μM-0.1 μM
反応時間 48 hours
実験の流れ 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, are cultured in RPMI-1640 media supplemented with 10% FBS, 4.5 g/L glucose, 1.5 g/L sodium bicarbonate, and Pen/Strep. Cells are passaged twice weekly. The inhibitory effect of Infigratinib (BGJ398) on BaF3 cell proliferation and viability is assessed using a Luciferase bioluminescent assay. Exponentially growing BaF3 or BaF3 Tel-TK cells are seeded into 384-well plates (4250 cells/well) at 50 μL/well using a μFill liquid dispenser in fresh medium. This compound is serially diluted in DMSO and arrayed in a polypropylene 384-well plate. Then 50 nL of it are transferred into the plates containing the cells by using the pintool transfer device, and the plates incubated at 37 °C (5% CO2) for 48 hours. Then 25 μL of Bright-Glo are added, and luminescence is quantified using an Analyst-GT. Custom curve-fitting software is used to produce a logistic fit of percent cell viability as a function of the logarithm of inhibitor concentration. The IC50 value is determined as the concentration needed to reduce cell viability to 50% of a DMSO control.
動物実験 動物モデル Athymic nude-nu mice bearing parental RT112 cell line
投薬量 10 mg/kg/qd and 30 mg/kg/qd
投与方法 Oral administration

参考

  • https://pubmed.ncbi.nlm.nih.gov/21936542/

カスタマーフィードバック

Data from [Hepatology, 2014, 59(4), 1427-34]

Data from [Hepatology, 2014, 59(4), 1427-34]

Data from [Data independently produced by J Cell Physiol, 2014, 229(11), 1647-59]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

3D-Printed Scaffolds Promote Enhanced Spinal Organoid Formation for Use in Spinal Cord Injury [ Adv Healthc Mater, 2025, e04817.] PubMed: 40702833
Selective degradation of FGFR1/2 overcomes antiestrogen resistance in ER+ breast cancer with FGFR1/2 alterations [ Cancer Lett, 2025, 619:217668] PubMed: 40127812
Abrogation of FGFR signaling blocks β-catenin-induced adrenocortical hyperplasia and aldosterone production [ JCI Insight, 2025, 10(21)e184863] PubMed: 40956622
Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion [ Breast Cancer Res, 2025, 27(1):132] PubMed: 40665359
Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas [ Commun Biol, 2025, 8(1):1185] PubMed: 40781553
Sonic hedgehog and fibroblast growth factor 8 regulate the evolution of amniote facial proportions [ Commun Biol, 2025, 8(1):84] PubMed: 39827295
Aspirin-triggered DHA metabolites inhibit angiogenesis [ Front Pharmacol, 2025, 16:1524980] PubMed: 40070577
Generation of an induced pluripotent stem cell line (NCHi023-A) from a 41-year-old male with nemaline myopathy carrying autosomal dominant ACTA1 c.809-10C>A mutation [ Stem Cell Res, 2025, 85:103701] PubMed: 40147060
Decaying and expanding Erk gradients process memory of skeletal size during zebrafish fin regeneration [ bioRxiv, 2025, 2025.01.23.634576] PubMed: 39896678
Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of ER+ breast cancer brain metastases in young and aged hosts [ bioRxiv, 2025, 2025.06.07.658373] PubMed: 40666846

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。