Infigratinib (BGJ398)
For research use only.
Catalog No.S2183 Synonyms: NVP-BGJ398
145 publications
CAS No. 872511-34-7
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.
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Biological Activity
| Description | 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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| In vitro |
BGJ398 also prevents VEGFR2 with low potency. The IC50 of BGJ398 for inhibiting VEGFR2 is 0.18 μM. BGJ398 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, BGJ398 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. BGJ398 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. BGJ398 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] |
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| Cell Data |
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| Assay |
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| In vivo | In this orthotopic xenograft bladder cancer model, 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 BGJ398 exhibits 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 BGJ398 at the doses of 4.25 and 8.51 mg/kg. BGJ398 significantly decreases the levels of pFRS2 and pMAPK in a dose-dependent manner. BGJ398 inhibits significantly bFGF-stimulated angiogenesis in a dose-dependent manner. However, BGJ398 does not impair VEGF-induced blood vessel formation. [1] |
Protocol
| Kinase Assay: [1] |
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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 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 minutes in a final volume of 30 μL including BGJ398. 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 the BGJ398. |
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| Cell Research:[1] |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | DMSO | 1 mg/mL warmed (1.78 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 1%CMC-Na For best results, use promptly after mixing. |
30mg/mL |
* 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.
Chemical Information
| Molecular Weight | 560.48 |
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| Formula | C26H31Cl2N7O3 |
| CAS No. | 872511-34-7 |
| Storage |
powder in solvent |
| Synonyms | NVP-BGJ398 |
| Smiles | CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl |
In vivo Formulation Calculator (Clear solution)
| Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment) | ||||||||||
| Dosage | mg/kg |  |
Average weight of animals | g | |
Dosing volume per animal | ul | |
Number of animals | |
| Step 2: Enter the in vivo formulation () | ||||||||||
| % DMSO % % Tween 80 % ddH2O | ||||||||||
| CalculateReset | ||||||||||
Calculation results:
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Bio Calculators
Molarity Calculator
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Dilution Calculator
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Molarity Calculator
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
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Question 1:
If you have any suggestions about the formulation of this compound for a direct oral gavage administration?
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Answer:
BGJ398 (S2183) can be dissolved in 30% PEG400/0.5% Tween80/5% Propylene glycol at 30 mg/ml as a suspension.
