Infigratinib (BGJ398)

別名：NVP-BGJ398

製品コード：S2183 純度：99.9%

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.

CAS No. 872511-34-7

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
10mg	JPY 29500	国内在庫あり
25mg	JPY 40500	国内在庫あり
100mg	JPY 85500	国内在庫あり
1g	JPY 145500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（229）

製品安全説明書

現在のバッチを見る：純度： 99.9%

99.9

Infigratinib (BGJ398)関連製品

関連ターゲット	FGFR1 FGFR2 FGFR3 FGFR4	もっと見る
関連製品	Fexagratinib (AZD4547) PD173074 BLU9931 LY2874455 Zoligratinib (Debio-1347) Futibatinib (TAS-120) PD-166866 SSR128129E H3B-6527 Fisogatinib (BLU-554) Derazantinib FIIN-2 Ferulic Acid ASP5878 Roblitinib (FGF401) Alofanib (RPT835) NSC12 PRN1371	もっと見る
関連化合物ライブラリー	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	もっと見る

シグナル伝達経路

FGFRシグナル伝達経路

FGFR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
SNU-C1	Growth Inhibition Assay	0.5-5 μM	48/72 h	no effect	24135816
HCT116	Growth Inhibition Assay	0.5-5 μM	48/72 h	decreases cell viability	24135816
HCD9	Growth Inhibition Assay	0.5-5 μM	48/72 h	decreases cell viability	24135816
HCC	Growth Inhibition Assay	1-2500 nM	48 h	IC50=1124 nm	25688743
HCC	Growth Inhibition Assay	1-2500 nM	48 h	IC50= 2359 nm	25688743
LS174T	Growth Inhibition Assay		48 h	IC50=4 μM	24503538
RKO	Growth Inhibition Assay		48 h	IC50=1.2 μM	24503538
HKH2	Growth Inhibition Assay		48 h	IC50=4 μM	24503538
HCT116	Growth Inhibition Assay		48 h	IC50=3 μM	24503538
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
SPAC1S	Growth Inhibition Assay			IC50=3.19 ± 0.93 μM	23443805
MFE296	Growth Inhibition Assay			IC50=2.86 ± 0.20 μM	23443805
HEC155	Growth Inhibition Assay			IC50=4.74 ± 1.09 μM	23443805
AN3CA	Growth Inhibition Assay			IC50=1.00 ± 0.20 μM	23443805
MFE280	Growth Inhibition Assay			IC50=2.63 ± 0.82 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
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生物活性

製品説明

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
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.
細胞実験	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. 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.
実験結果図	Methods	Biomarkers	結果図	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]
動物実験	動物モデル	Athymic nude-nu mice bearing parental RT112 cell line
	投与量	10 mg/kg/qd and 30 mg/kg/qd
	投与経路	Oral administration

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考
[1] Guagnano V, et al. J Med Chem. 2011, 54(20), 7066-7083.

参考

[1] Guagnano V, et al. J Med Chem. 2011, 54(20), 7066-7083.

化学情報

分子量	560.48	化学式	C₂₆H₃₁Cl₂N₇O₃
CAS No.	872511-34-7	SDF	Download Infigratinib (BGJ398) SDFをダウンロードする
Smiles	CCN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 27 mg/mL ( (48.17 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問（FAQ）

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

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

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):