Nintedanib (BIBF 1120)

製品コードS1010 別名:Intedanib

Nintedanib (BIBF 1120)化学構造

分子量(MW):539.62

Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.

サイズ 価格(税別)  
JPY 21900
JPY 36800
JPY 113200
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バルク問合せ

文献中Selleckの製品使用例(31)

製品安全説明書

VEGFR阻害剤の選択性比較

生物活性

製品説明 Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.
ターゲット
VEGFR2 [1]
(Cell-free assay)
VEGFR3 [1]
(Cell-free assay)
LCK [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
VEGFR1 [1]
(Cell-free assay)
13 nM 13 nM 16 nM 26 nM 34 nM
体外試験

BIBF1120 inhibits PDGFR kinase activity of PDGFR alpha and PDGFR beta types with IC50 values of 59 nM and 65 nM, respectively. In addition, BIBF1120 suppresses the FGFR subtypes with IC50 of 60 nM, 37 nM and 108 nM for FGFR1, FGFR2, and FGFR3, respectively. BIBF1120 binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. The indolinone scaffold forms two hydrogen bonds with the backbone nitrogen of Cys919 and the backbone carbonyl oxygen of Glu917 in the hinge region. BIBF 1120 inhibits proliferation of PDGF-BB stimulated BRPs with EC50 of 79 nM in cell assays. BIBF1120 at concentrations as low as 100 nM blocks activation of MAPK after stimulation with 5% serum plus PDGF-BB. In cultures of human vascular smooth muscle cells (HUASMC), BIBF1120 prevents PDGF-BB stimulated proliferation with an EC50 of 69 nM. [1]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SKOV3 NYr1WJUyTnWwY4Tpc44hSXO|YYm= MmDWOUDDvU1? NV7NbGxCOjRiaB?= NGLVc2JFVVOR MljZbY5lfWOnczDhJJNq\26rZnnjZY51KGmwY4LlZZNmKGmwIITo[UBxem:vb4TldkBi[3Srdnn0bYV{KG:oIFWtZ4FlNMLiQ1TINUwh[W6mwrDDSGg{ MVmyOlA3OTd2Nx?=
A549 MnvuSpVv[3Srb36gRZN{[Xl? NHHVPJozNzVizszN MW[yOEBp MVTEUXNQ MXfoZZMh[SCpZX7ldoFtKEWPVDDy[ZZmenOjbDDl[oZm[3UEoB?= M4XmZVI3ODZzN{S3
T24 MkjjSpVv[3Srb36gRZN{[Xl? M1HUeVIwPSEQvF2= NUPIfJRMOjRiaB?= MmjvSG1UVw>? MnT6bIF{KGFiZ3Xu[ZJidCCHTWSgdoV3\XK|YXyg[YZn\WO2wrC= NFfvelEzPjB4MUe0Oy=>
Mia-Paca2 NIjTdY1HfW6ldHnvckBCe3OjeR?= M1jhOlIwPSEQvF2= MmjwNlQhcA>? M4LS[mROW09? MXzoZZMh[SCpZX7ldoFtKEWPVDDy[ZZmenOjbDDl[oZm[3UEoB?= NY[0UG1iOjZyNkG3OFc>
A549 NV7rbpNyTnWwY4Tpc44hSXO|YYm= NV30VVQ2OC5yMfMAl|XDqM7:TR?= NXzkcXJqOjRiaB?= NYfYVGp1TE2VTx?= MUjpcoR2[2W|IGPGWHBFyqCvUl7BJIV5eHKnc4Ppc44h\G:|ZTDk[ZBmdmSnboTsfS=> NV3aV3BkOjV6NEOwNFU>
A549 NE\1[FZHfW6ldHnvckBCe3OjeR?= NW\XTYMzOC5yMfMAl|XDqM7:TR?= Mn\hO|IhcA>? NXrCUlFQTE2VTx?= NFfCU4ZmdmijbnPld{BUWC2GIIDyc5RmcW5iZYjwdoV{e2mxbjDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6ncjDheEBkd26lZX70doF1cW:wczDv[kB2eCC2bzC1xsDPxE4EoB?= NEHQe5YzPTh2M{CwOS=>
A549 Mof4SpVv[3Srb36gRZN{[Xl? Mlu5OeKh|ryP NInuXnUxNTFiaB?= MlrwSG1UVw>? NInJN2FqdmO{ZXHz[ZMhSVBvMTDhZ5RqfmG2aX;uJEBi\nSncjCzNEBucW5? NX\CeJhQOjV6NEOwNFU>
Hep3B NWPJb|F6S2WubDDWbYFjcWyrdImgRZN{[Xl? NV\aPHN{OC1{MDFOwG0> Mo\xOFjDqGh? MV7k[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHliZH;z[UBl\XCnbnTlcpRtgQ>? NIH2OFkzPDZ3N{O5PC=>
HepG2 MVzD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUGwMVIxKM7:TR?= MY[0POKhcA>? MVXk[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHliZH;z[UBl\XCnbnTlcpRtgQ>? NX:wcnA5OjR4NUezPVg>
PLC5 NHrodWlE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MmTjNE0zOCEQvF2= NYLiWJZYPDkEoHi= MWDk[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHliZH;z[UBl\XCnbnTlcpRtgQ>? M1jQPFI1PjV5M{m4
HuH7 M4Gw[WNmdGxiVnnhZoltcXS7IFHzd4F6 MU[wMVIxKM7:TR?= NIjQfpA1QMLiaB?= M1rhbYRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDkc5NmKGSncHXu[IVvfGy7 M2GwT|I1PjV5M{m4
SK-Hep1 M1fYU2NmdGxiVnnhZoltcXS7IFHzd4F6 MXewMVIxKM7:TR?= NYrjWlZnPDkEoHi= NYD0[WtX\GWlcnXhd4V{KGOnbHygeoli[mmuaYT5JIRwe2ViZHXw[Y5l\W62bIm= MVOyOFY2PzN7OB?=
Hep3B NH\2[FlCeG:ydH;zbZMhSXO|YYm= MVGwMVIxKM7:TR?= MnrHOFjDqGh? Ml3GbY5lfWOnczDj[YxtKGGyb4D0c5NqeyCmb4PlJIRmeGWwZHXueIx6 MV[yOFY2PzN7OB?=
HepG2 MWfBdI9xfG:|aYOgRZN{[Xl? NGXjW5AxNTJyIN88US=> NXfLcJhjPDkEoHi= MoTnbY5lfWOnczDj[YxtKGGyb4D0c5NqeyCmb4PlJIRmeGWwZHXueIx6 MX2yOFY2PzN7OB?=
PLC5 M4rpN2Fxd3C2b4Ppd{BCe3OjeR?= MlfuNE0zOCEQvF2= NWXpTIg4PDkEoHi= MX3pcoR2[2W|IHPlcIwh[XCxcITvd4l{KGSxc3Wg[IVx\W6mZX70cJk> M4DYfFI1PjV5M{m4
HuH7 M1XWfGFxd3C2b4Ppd{BCe3OjeR?= NXzie25iOC1{MDFOwG0> NVvSVZZYPDkEoHi= MVTpcoR2[2W|IHPlcIwh[XCxcITvd4l{KGSxc3Wg[IVx\W6mZX70cJk> M{THSlI1PjV5M{m4
SK-Hep1 NE[5V2dCeG:ydH;zbZMhSXO|YYm= MnS2NE0zOCEQvF2= M{G4dlQ5yqCq MUTpcoR2[2W|IHPlcIwh[XCxcITvd4l{KGSxc3Wg[IVx\W6mZX70cJk> MXuyOFY2PzN7OB?=
H1703 NHP6XWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4TUNWlEPTB;MD6wOUDPxE1? M4DrWVI{PzJ7NECz

他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

アッセイ
Methods Test Index PMID
Western blot
Fibronectin / Collagen 1a1; 

PubMed: 26072676     


(A and B) IPF fibroblasts were treated with increasing doses of nintedanib (0.5, 1, or 2 μM) (A) or nintedanib (2 μM) for increasing durations (24, 48, or 72 h) (B). Expression of fibronectin and collagen 1a1 was evaluated by Western immunoblotting.

p-SMAD3 / SMAD3 / p-p38 MAPK / p38 MAPK ; 

PubMed: 26072676     


IMR-90 fibroblasts were serum starved overnight and cotreated with or without TGF-β1 (2.5 ng/ml) and increasing doses of nintedanib (0.5, 1, and 2 μM) for 1 hour. Expression of pS423/425-SMAD3, SMAD3, pT180/Y182-p38 mitogen-activated protein kinase (MAPK), and p38 MAPK was evaluated by Western blotting. 

Cyclin A / Cyclin D1 / Cyclin E / CDK2 / CDK4 / CDK6; 

PubMed: 29934570     


Western blot based detection of cell cycle associated molecules viz., Cyclins A, D1 and E, and CDKs 2, 4 and 6 in PC3 cells after 72 hours of Nintedanib treatment. 

p-EGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK; 

PubMed: 27581340     


Effects of nintedanib on FGFR1, ERK, and AKT phosphorylation in FGFR1 CNG‐positive lung squamous cell carcinoma cell lines. H520 and LK‐2 cells were incubated for 6 h in the presence of the indicated concentrations of nintedanib, after which cell lysates (25 μg soluble protein) were subjected to immunoblot analysis with antibodies to the indicated proteins.

26072676 29934570 27581340
Immunofluorescence
Vimentin / E-cadherin ; 

PubMed: 29934570     


Immunoflouresence staining for Vimentin (green) and E-cadherin (red) in DMSO control and 2.5 µM Nintedanib treated PC3 cells after 72 h of incubation. Representative flourescent pictures are shown at 600X. DAPI: 4′,6-diamidino-2-phenylindole.

29934570
体内試験 In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF1120 is highly active at well-tolerated doses (25-100 mg/kg daily p.o.). This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth inhibition. [1]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[3]
+ 展開

VEGFR2 Kinase Assay:

The cytoplasmic tyrosine kinase domain of VEGFR2 (residues 797-1355 according to sequence deposited in databank SWISS-PROT P35968) is cloned into pFastBac fused to GST and extracted. Enzyme activity is assayed in the presence or absence of serial dilutions of BIBF1120 performed in 25% DMSO. Each microtiter plate contains internal controls such as blank, maximum reaction, and historical reference compound. All incubations are conducted at room temperature on a rotation shaker. 10 μL of each BIBF1120 dilution is added to 10 μL of diluted kinase (0.8 μg/mL VEGFR2, 10 mM Tris pH 7.5, 2 mM EDTA, and 2 mg/mL BSA) and preincubated for 1 hour. The reaction is started by addition of 30 μL of substrate mix containing 62.4 mM Tris pH 7.5, 2.7 mM DTT, 5.3 mM MnCl2, 13.3 mM Mg-acetate, 0.42 mM ATP, 0.83 mg/mL Poly-Glu-Tyr(4:1), and 1.7 μg/mL Poly-Glu-Tyr(4:1)-biotin and incubated for 1 hour. The reaction is stopped by addition of 50 μL of 250 mM EDTA, 20 mM HEPES, pH 7.4. 90 μL of the reaction mix is transferred to a streptavidin plate and incubated for 1-2 hours. After three washes with PBS the EU-labeled antibody, PY20 is added (recommended dilution 1:2000 of 0.5 mg/mL labeled antibody in DELFIA assay buffer). Excessive detection antibody is removed by three washes of DELFIA washing buffer. Then 10 minutes before measurement on the multilabel reader, each well is incubated with 100 μL of DELFIA enhancement solution.
細胞試験: [1]
+ 展開
  • 細胞株: HUVEC, HUASMC, and BRP cell lines
  • 濃度: 50 nM
  • 反応時間: 2 hours
  • 実験の流れ: The cell lines HUVEC, HUASMC, and BRP are used for the assay. BIBF1120 is added to the cultures two hours before the addition of ligands. Cell lysates are generated. Western blotting is done using standard SDS-PAGE methods, loading 50 to 75 μg of protein per lane. Detection is facilitated by enhanced chemiluminescence. Total and phosphorylated mitogen-activated protein kinase (MAPK) is analyzed using monoclonal antibodies M3807 and M8159. Total Akt is detected using the corresponding polyclonal antibody and phosphorylated Akt (Ser473) is analyzed by using its monoclonal antibody. Monoclonal antibody is also used to detect cleaved caspase-3 while KDR (VEGFR2) protein is detected using a corresponding antibody.
    (参考用のみ)
動物試験:[1]
+ 展開
  • 動物モデル: FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 xenografts in Athymic NMRI-nu/nu female mice
  • 製剤: In a 0.5 % Natrosol solution
  • 投薬量: 100 mg/kg
  • 投与方法: p.o.
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 6 mg/mL (11.11 mM)
Ethanol 3 mg/mL (5.55 mM)
Water Insoluble
体内 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
5% DMSO+40% PEG 300+2% Tween 80+ddH2O
混合させたのち直ちに使用することを推奨します。
0.25mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 539.62
化学式

C31H33N5O4

CAS No. 656247-17-5
保管
in solvent
別名 Intedanib

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (mg) = 濃度 (mM) x 体積 (mL) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03710824 Recruiting Drug: Nintedanib Idiopathic Pulmonary Fibrosis Boehringer Ingelheim February 28 2019 --
NCT03958071 Completed Drug: Nintedanib|Drug: Pirfenidone|Other: Untreated Cohort Idiopathic Pulmonary Fibrosis Boehringer Ingelheim December 19 2018 --
NCT03283007 Not yet recruiting Drug: Nintedanib|Drug: Placebo Lung-transplant Recipients Assistance Publique - Hôpitaux de Paris October 2018 Phase 3
NCT03725852 Recruiting Drug: GLPG1205|Drug: Placebo Idiopathic Pulmonary Fibrosis Galapagos NV September 27 2018 Phase 2
NCT03287947 Recruiting Drug: nintedanib Appendix Cancer Jimmy Hwang|Boehringer Ingelheim|Atrium Health November 10 2017 Phase 2
NCT02182102 Completed Drug: BIBF 1120|Drug: Pemetrexed Carcinoma Non-Small-Cell Lung Boehringer Ingelheim September 2005 Phase 1

技術サポート

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Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

  • * 必須

VEGFRシグナル伝達経路

VEGFR Inhibitors with Unique Features

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID