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Quality Control

Batch: Purity: 99.87%

99.87

Products Often Used Together with BGJ398 (Infigratinib)

Varlitinib

It and Varlitinib show a potent antitumor effect and can effectively overcome resistance to this compound.

SAR131675

It and SAR131675 completely inhibit lymphangiogenesis and significantly suppress tumor growth and progression in lymphatic endothelial cells (LECs).

Related Targets	EGFR VEGFR JAK PDGFR Src HIF FLT FLT3 HER2 Bcr-Abl
Other FGFR Inhibitors	PD173074 AZD4547 (Fexagratinib) BLU9931 H3B-6527 Futibatinib (TAS-120) LY2874455 PD-166866 Zoligratinib (Debio-1347) SSR128129E Fisogatinib (BLU-554)

Cell Culture, Treatment & Working Concentration

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

Solubility

In vitro
Batch:

DMSO : 3 mg/mL (5.35 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
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.
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.
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.
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.
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.

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

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 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.

Chemical Information, Storage & Stability

Molecular Weight	560.48	Formula	C₂₆H₃₁Cl₂N₇O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	872511-34-7	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin 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

Mechanism of Action

Targets/IC₅₀/Ki	FGFR1 (Cell-free assay) 0.9 nM FGFR3 (Cell-free assay) 1.0 nM FGFR2 (Cell-free assay) 1.4 nM FGFR3 (K650E) (Cell-free assay) 4.9 nM FGFR4 (Cell-free assay) 60 nM
In vitro	Infigratinib (BGJ398) also prevents VEGFR2 with low potency, with an IC50 of 0.18 μM for inhibiting this target. It suppresses other kinases including ABL, FYN, KIT, LCK, LYN and YES with IC50 values 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, this compound 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. Additionally, 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.
Kinase Assay	Radiometric kinase assay
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.
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 this compound 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 Infigratinib (BGJ398) 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. Additionally, it inhibits significantly bFGF-stimulated angiogenesis in a dose-dependent manner. However, it does not impair VEGF-induced blood vessel formation.
References	[1] https://pubmed.ncbi.nlm.nih.gov/21936542/

Applications

Methods	Biomarkers	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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

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

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

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C7=C6/X	C7:	LOG(C7):
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BGJ398 (Infigratinib) FGFR inhibitor

Chemical Structure

Molecular Weight: 560.48