Home Protein Tyrosine Kinase VEGFR inhibitor - FGFR inhibitor - PDGFR inhibitor - Src inhibitor Nintedanib For research use only.

Nintedanib

Synonyms: BIBF 1120, Intedanib

Nintedanib 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.

Nintedanib Chemical Structure

Nintedanib Chemical Structure

CAS No. 656247-17-5

Purity & Quality Control

Nintedanib Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SKOV3 Function Assay 5 µM 24 h DMSO induces a significant increase in the promoter activities of E-cad, CDH1, and CDH3 26061747
A549 Function Assay 2/5 μM 24 h DMSO has a general EMT reversal effect  26061747
T24 Function Assay 2/5 μM 24 h DMSO has a general EMT reversal effect  26061747
Mia-Paca2 Function Assay 2/5 μM 24 h DMSO has a general EMT reversal effect  26061747
A549 Function Assay 0.01–5 μM 24 h DMSO induces SFTPD mRNA expression dose dependently 25843005
A549 Function Assay 0.01–5 μM 72 h DMSO enhances SP-D protein expression in a dose-dependent manner at concentrations of up to 5 μM  25843005
A549 Function Assay 5 μM 0-1 h DMSO increases AP-1 activation after 30 min 25843005
Hep3B Cell Viability Assay 0-20 μM 48 h decreases cell viability dose dependently 24657398
HepG2 Cell Viability Assay 0-20 μM 48 h decreases cell viability dose dependently 24657398
PLC5 Cell Viability Assay 0-20 μM 48 h decreases cell viability dose dependently 24657398
HuH7 Cell Viability Assay 0-20 μM 48 h decreases cell viability dose dependently 24657398
SK-Hep1 Cell Viability Assay 0-20 μM 48 h decreases cell viability dose dependently 24657398
Hep3B Apoptosis Assay 0-20 μM 48 h induces cell apoptosis dose dependently 24657398
HepG2 Apoptosis Assay 0-20 μM 48 h induces cell apoptosis dose dependently 24657398
PLC5 Apoptosis Assay 0-20 μM 48 h induces cell apoptosis dose dependently 24657398
HuH7 Apoptosis Assay 0-20 μM 48 h induces cell apoptosis dose dependently 24657398
SK-Hep1 Apoptosis Assay 0-20 μM 48 h induces cell apoptosis dose dependently 24657398
H1703 Growth Inhibition Assay IC50=0.05 μM 23729403
Sf9 Function assay 20 mins Inhibition of mouse GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.013 μM. 18559524
Sf9 Function assay 20 mins Inhibition of human GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.021 μM. 18559524
NIH3T3 Function assay 50 nM 1 hr Inhibition of VEGFR2 transfected in mouse NIH3T3 cells at 50 nM incubated for 1 hr measured after 32 hrs washout followed by VEGF stimulation for 10 mins by Western blotting 18559524
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 4.9 μM. 28190652
SKOV3 Antiproliferative assay 72 hrs Antiproliferative activity against human SKOV3 cells after 72 hrs by MTT assay, IC50 = 28.76 μM. 28190652
BL21 (DE3) Function assay 30 mins Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, Ki = 0.0056 μM. 28351607
BL21 (DE3) Function assay 30 mins Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, IC50 = 0.043 μM. 28351607
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.83 μM. 28826084
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 8.28 μM. 28826084
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 22.62 μM. 28826084
NIH/3T3 Function assay 42 hrs Inhibition of PDGFR in mouse NIH/3T3 cells assessed as reduction in recombinant human PDGF-BB-induced cell proliferation after 42 hrs by cell titer 96 aqueous one solution based assay, IC50 = 0.085 μM. 29152045
Sf9 Function assay Inhibition of human VEGFR2 expressed in Sf9 cells, IC50 = 0.005 μM. 19522465
NIH3T3 Function assay 1 hr Inhibition of VEGF-stimulated human VEGFR2 phosphorylation expressed in mouse NIH3T3 cells pretreated for 1 hr measured 32 hrs after drug dose by immunoprecipitation based pulse-chase experiment 19522465
BRP Apoptosis assay Induction of apoptosis in BRP cells assessed as caspase-3 cleavage 19522465
BRP Antiangiogenic assay Antiangiogenic activity BRP cells assessed as inhibition of cell proliferation by [3H]thymidine incorporation assay 19522465
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description Nintedanib 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.
Targets
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)		 Click to View More Targets
13 nM 13 nM 16 nM 26 nM 34 nM
In vitro
In vitro

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]
Kinase Assay 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.
Cell Research Cell lines HUVEC, HUASMC, and BRP cell lines
Concentrations 50 nM
Incubation Time 2 hours
Method

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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-EGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK Cyclin A / Cyclin D1 / Cyclin E / CDK2 / CDK4 / CDK6 p-SMAD3 / SMAD3 / p-p38 MAPK / p38 MAPK Fibronectin / Collagen 1a1 27581340
Immunofluorescence Vimentin / E-cadherin 29934570
In Vivo
In vivo

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]
Animal Research Animal Models FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 xenografts in Athymic NMRI-nu/nu female mice
Dosages 100 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06200714 Recruiting
Idiopathic Pulmonary Fibrosis|Diarrhoea
Boehringer Ingelheim
 April 30 2024 --
NCT05676112 Withdrawn
Pulmonary Fibrosis
Boehringer Ingelheim|China-Japan Friendship Hospital
 December 29 2023 --
NCT06070610 Completed
Healthy
Boehringer Ingelheim
 November 8 2023 Phase 1
NCT05755308 Not yet recruiting
Idiopathic Pulmonary Fibrosis
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
 October 2023 Not Applicable
NCT06071013 Not yet recruiting
Non-small Cell Lung Cancer|EGFR Gene Mutation|EGFR-TKI Resistant Mutation
China Medical University Hospital
 September 28 2023 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 539.62 Formula

C31H33N5O4
CAS No. 656247-17-5 SDF Download Nintedanib SDF
Smiles CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O
Storage (From the date of receipt)

In vitro
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DMSO : 10 mg/mL ( (18.53 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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