Home Angiogenesis FGFR inhibitor Infigratinib (BGJ398) For research use only.

Infigratinib (BGJ398)

Synonyms: NVP-BGJ398

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.

Infigratinib (BGJ398) Chemical Structure

Infigratinib (BGJ398) Chemical Structure

CAS No. 872511-34-7

Purity & Quality Control

Infigratinib (BGJ398) Related Products

Signaling Pathway

FGFR Signaling Pathways

FGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCC Growth Inhibition Assay 1-2500 nM 48 h IC50= 2359 nm 25688743
HCC Growth Inhibition Assay 1-2500 nM 48 h IC50=1124 nm 25688743
HCT116 Growth Inhibition Assay 48 h IC50=3 μM 24503538
HKH2 Growth Inhibition Assay 48 h IC50=4 μM 24503538
RKO Growth Inhibition Assay 48 h IC50=1.2 μM 24503538
LS174T Growth Inhibition Assay 48 h IC50=4 μM 24503538
HCD9 Growth Inhibition Assay 0.5-5 μM 48/72 h DMSO decreases cell viability 24135816
HCT116 Growth Inhibition Assay 0.5-5 μM 48/72 h DMSO decreases cell viability 24135816
SNU-C1 Growth Inhibition Assay 0.5-5 μM 48/72 h DMSO no effect 24135816
MFE280 Growth Inhibition Assay IC50=2.63 ± 0.82 μM 23443805
AN3CA Growth Inhibition Assay IC50=1.00 ± 0.20 μM 23443805
HEC155 Growth Inhibition Assay IC50=4.74 ± 1.09 μM 23443805
MFE296 Growth Inhibition Assay IC50=2.86 ± 0.20 μM 23443805
SPAC1S Growth Inhibition Assay IC50=3.19 ± 0.93 μM 23443805
RL952 Growth Inhibition Assay IC50=3.41 ± 0.23 μM 23443805
EN1 Growth Inhibition Assay IC50=4.75 ± 0.62 μM 23443805
SNGII Growth Inhibition Assay IC50=4.29 ± 0.58 μM 23443805
ISHIKAWA Growth Inhibition Assay IC50=5.48 ± 0.03 μM 23443805
HEC1A Growth Inhibition Assay IC50=10.00 ± 1.00 μM 23443805
KLE Growth Inhibition Assay IC50=3.03 ± 0.11 μM 23443805
SNGM Growth Inhibition Assay IC50=5.00 ± 0.41 μM 23443805
USPC2 Growth Inhibition Assay IC50=7.00 ± 0.21 μM 23443805
EN Growth Inhibition Assay IC50=6.03 ± 0.31 μM 23443805
MFE319 Growth Inhibition Assay IC50=5.37 ± 0.03 μM 23443805
EFE184 Growth Inhibition Assay IC50=8.04 ± 0.69 μM 23443805
ECC1 Growth Inhibition Assay IC50=6.74 ± 0.59 μM 23443805
HEC1B Growth Inhibition Assay IC50=6.45 ± 0.67 μM 23443805
USPC1 Growth Inhibition Assay IC50=5.75 ± 0.50 μM 23443805
SPAC1L Growth Inhibition Assay IC50=4.92 ± 0.50 μM 23443805
HCC827 Function assay Displacement of [3H]-cyclopamine from SMO V404M mutant in gefitinib resistant human HCC827 cells by scintillation counting, Ki = 0.0465 μM. 28787156
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
sf9 Function assay 60 mins Inhibition of non-phosphorylated N-terminal His6-tagged FGFR4 C552A mutant (G442 to E753 residues) (unknown origin) expressed in sf9 cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 as substrate after 60 mins by microfluidic mobility shift assay, IC50 = 0.00082 μM. ChEMBL
sf9 Function assay 60 mins Inhibition of wild type non-phosphorylated N-terminal His6-tagged FGFR4 (G442 to E753 residues) (unknown origin) expressed in sf9 cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 as substrate after 60 mins by microfluidic mobility shift assay, IC50 = 0.062 μM. ChEMBL
sf9 Function assay 60 mins Inhibition of non-phosphorylated N-terminal His6-tagged FGFR4 C477A mutant (G442 to E753 residues) (unknown origin) expressed in sf9 cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 as substrate after 60 mins by microfluidic mobility shift assay, IC50 = 0.064 μM. ChEMBL
Click to View More Cell Line Experimental Data

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.
Targets
FGFR1 [1]
(Cell-free assay)		 FGFR3 [1]
(Cell-free assay)		 FGFR2 [1]
(Cell-free assay)		 FGFR3 (K650E) [1]
(Cell-free assay)		 FGFR4 [1]
(Cell-free assay)
0.9 nM 1.0 nM 1.4 nM 4.9 nM 60 nM
In vitro
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]
Kinase Assay 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.
Cell Research Cell lines Murine BaF3 cell lines
Concentrations 0 μM-0.1 μM
Incubation Time 48 hours
Method 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. BGJ398-mediated inhibition of 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. BGJ398 is serially diluted in DMSO and arrayed in a polypropylene 384-well plate. Then 50 nL of BGJ398 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 of BGJ398 needed to reduce cell viability to 50% of a DMSO control.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pFGFR1 / FGFR1 / pFRS2 / FRS2 / MEK / ERK p-YAP (S127) / YAP Mcl-1 Cyclin D1 / Cyclin A / Cyclin B / γ-H2AX / Cleaved caspase-9 / PARP Snail / Slug / ZEB1 p-FRS2 / FRS2 / p-AKT / AKT / p-ERK / ERK 28255027
Immunofluorescence YAP 26826125
Growth inhibition assay Cell viability IC50 28255027
In Vivo
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]
Animal Research Animal Models Athymic nude-nu mice bearing parental RT112 cell line
Dosages 10 mg/kg/qd and 30 mg/kg/qd
Administration Oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03510455 Terminated
Tumor-Induced Osteomalacia|Oncogenic Osteomalacia
National Institute of Dental and Craniofacial Research (NIDCR)|National Institutes of Health Clinical Center (CC)
 February 27 2019 Phase 2
NCT02312804 Withdrawn
Cancer of Cervix|Tumors
The University of Texas Health Science Center at San Antonio
 January 2015 Phase 1
NCT02160041 Terminated
Solid Tumor|Hematologic Malignancies
Novartis Pharmaceuticals|Novartis
 July 24 2014 Phase 2
NCT01928459 Completed
Advanced Solid Tumors|Metastatic Solid Tumors
Novartis Pharmaceuticals|Novartis
 October 2013 Phase 1
NCT01004224 Completed
Advanced Solid Tumors With Alterations of FGFR1 2 and or 3|Squamous Lung Cancer With FGFR1 Amplification|Bladder Cancer With FGFR3 Mutation or Fusion|Advanced Solid Tumors With FGFR1 Amplication|Advanced Solid Tumors With FGFR2 Amplication|Advanced Solid Tumors With FGFR3 Mutation
Novartis Pharmaceuticals|Novartis
 December 11 2009 Phase 1

Chemical Information & Solubility

Molecular Weight 560.48 Formula

C26H31Cl2N7O3
CAS No. 872511-34-7 SDF Download Infigratinib (BGJ398) SDF
Smiles CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 27 mg/mL ( (48.17 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Frequently Asked Questions

Question 1:
If you have any suggestions about the formulation of this compound for a direct oral gavage administration?

Answer:
BGJ398 (S2183) can be dissolved in 30% PEG400/0.5% Tween80/5% Propylene glycol at 30 mg/ml as a suspension.

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