BGJ398 (NVP-BGJ398)
Catalog No.S2183
Molecular Weight(MW): 560.48
BGJ398 (NVP-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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5 Customer Reviews
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Activation of FGFR2 and MAPK by FGFR2-AHCYL1 and its suppression by FGFR inhibitors. Lysates from NIN3T3 cells expressing FGFR2-AHCYL1 or EZR-ROS1 (control) treated with vehicle (DMSO), 0.2 and 1 µM BGJ398, and 0.2 and 1 µM PD173074 were immunoblotted with the relevant antibodies. β-actin was used as a loading control.
Hepatology 2014 59(4), 1427-34. BGJ398 (NVP-BGJ398) purchased from Selleck.
Anchorage-independent growth of NIN3T3 cells expressing FGFR2 fusions and its suppression by FGFR inhibitors (BGJ: BGJ398 and PD: PD173074). The percentage (+/- s.d.) of colonies formed in the presence of FGFR2 inhibitors (0.2 礛) and by KD mutants with respect to those formed by DMSO-treated cells are plotted at the bottom. The NIH3T3 clone expressing EZR-ROS1 was used as a negative control for FGFR inhibitors. *P<0.05.
Hepatology 2014 59(4), 1427-34. BGJ398 (NVP-BGJ398) purchased from Selleck.
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we used a FGFR inhibitor (BGJ398) and a MEK inhibitor (PD98059) to confirm that the inhibition of FGF pathway was directly related to the fibroblast-like conversion, and same morphologic change and increased expression of Vim and COL I was observed
Oncogene, 2017, 36(27):3831-3841. BGJ398 (NVP-BGJ398) purchased from Selleck.
BGJ398 inhibits signaling in cell lines with activating FGFR alterations. Immunoblot demonstrates the expression of total/pFGFRs and total/pFRS2 in DMSO and BGJ398 in treated cell lines (A) DMS114. B, RT112. Lysates were prepared from cells exposed to BGJ398 (at the indicated concentrations) for 24 hours and immunoblots performed with the respective antibodies. Representative data are shown from three experimental replicates. Bar graphs display densitometric analysis of protein bands using GAPDH as a control. BGJ398 treatment results in decreased levels of pFGFR1/pFGFR3 and pFRS2/total FRS2, respectively.
Mol Cancer Ther, 2017, 16(4):614-624. BGJ398 (NVP-BGJ398) purchased from Selleck.
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BGJ39 distinctly inhibited the inductive effect of FGF2. Just as the results of western blot, BGJ39 not only reversed the down-expression of E-cadherin, but also weakened the expression of BSP and OPN. However, combination of both TGF- β1 and FGF2 containing BGJ39 distinctly improved the expression of fibronectin and periostin. β-actin was used as an internal control for equal protein loading. * P < 0.05, ** P < 0.01.
J Cell Physiol 2014 229(11), 1647-59. BGJ398 (NVP-BGJ398) purchased from Selleck.
Purity & Quality Control
Choose Selective FGFR Inhibitors
Biological Activity
| Description | BGJ398 (NVP-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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| 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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| 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 | N/A |
Bio Calculators
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT03510455 | Not yet recruiting | Tumor-Induced Osteomalacia | National Institute of Dental and Craniofacial Research (NIDCR)|National Institutes of Health Clinical Center (CC) | November 20 2018 | Phase 2 |
| NCT02706691 | Recruiting | FGFR Gene Amplification|FGFR1 Gene Amplification|FGFR2 Gene Amplification|FGFR2 Gene Mutation|FGFR3 Gene Mutation|Head and Neck Squamous Cell Carcinoma|Human Papillomavirus Infection|Recurrent Head and Neck Carcinoma|Recurrent Nasopharynx Carcinoma|Recurrent Oropharyngeal Squamous Cell Carcinoma | University of Chicago|Novartis | June 1 2018 | Phase 2 |
| NCT02657486 | Recruiting | Bladder Cancer|Non-Muscle-Invasive Urothelial Carcinoma | Memorial Sloan Kettering Cancer Center | January 2016 | Not Applicable |
| NCT02312804 | Withdrawn | Cancer of Cervix|Tumors | The University of Texas Health Science Center at San Antonio | January 2015 | Phase 1 |
| NCT02257541 | Active not recruiting | Advanced Gastrointestinal Stromal Tumor (GIST) | Memorial Sloan Kettering Cancer Center|Dana-Farber Cancer Institute|M.D. Anderson Cancer Center|University of Pittsburgh | October 2 2014 | Phase 1|Phase 2 |
| NCT02160041 | Completed | Solid Tumor|Hematologic Malignancies | Novartis Pharmaceuticals|Novartis | July 24 2014 | Phase 2 |
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.
