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Nintedanib (BIBF 1120)

Multi-target kinase inhibitor, inhibits VEGFR, PDGFR, and FGFR

Nintedanib (BIBF 1120)

Catalog No. A8252
Size Price Stock Qty
Evaluation Sample $28.00  All Inclusive In stock
5mg $90.00 In stock
25mg $177.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

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Chemical structure

Nintedanib(BIBF 1120)

Related Biological Data

Nintedanib(BIBF 1120)

Related Biological Data

Nintedanib(BIBF 1120)

Biological Activity

Description Nintedanib (BIBF 1120) is a potent inhibitor of triple angiokinase 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, respectively.
Targets VEGFR1/2/3 FGFR1/2/3 PDGFRα/β      
IC50 34 nM/13 nM/13 nM 69 nM/37 nM/108 nM 59 nM/65 nM      

Protocol

Cell experiment: [1]

Cell lines

PLC5, Hep3B, SK-Hep1, HuH7 and HepG2 cells

Preparation method

This product is soluble in DMSO mostly at 11 mM. It is also soluble in water with no more than 1 mM. Stock solution can be stored at -80 °C less than 6 months.

Reacting condition

20 μM, 48 hours

Applications

Cell viability was determined by MTT assay after treatment for 48 h. Nintedanib significantly induced the accumulation of sub-G1-positive cells in all the tested HCC cells. Further, induction of apoptosis by nintedanib was also demonstrated by DNA fragmentation assay. Nintedanib exhibited a significant ratio of induction of DNA fragmentation at clinically relevant concentrations in a dose-dependent manner for all of the five HCC cell lines.

Animal experiment: [2]

Animal models

Female NOD/SCID mice injected with A459, Calu-6 or H1993 cells

Dosage form

Oral administration, 50 mg/kg 5 days a week

Application

In A549 xenografts, the single-agent therapy of BIBF 1120 effectively reduced primary tumor size in each setting. For all the three xenografts, a decrease in tumor growth rate was observed across all models, particularly in the combination groups, where the growth curve gradually became linear. End tumor volumes and weights were lower in BIBF 1120 and the combination groups compared to controls, across all models. In A549 and H1993 xenografts, combination was more effective than single agent therapy; however, in Calu-6 xenografts combination therapy was not different from BIBF 1120 single agent therapy.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Tai W T, Shiau C W, Li Y S, et al. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. Journal of hepatology, 2014.

[2] Cenik B K, Ostapoff K T, Gerber D E, et al. BIBF 1120 (nintedanib), a triple angiokinase inhibitor, induces hypoxia but not EMT and blocks progression of preclinical models of lung and pancreatic cancer. Molecular cancer therapeutics, 2013, 12(6): 992-1001.

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Chemical Properties

Cas No. 928326-83-4 SDF Download SDF
Synonyms Vargatef
Chemical Name methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate
Canonical SMILES CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)NC(=C3C4=C(C=C(C=C4)C(=O)OC)NC3=O)C5=CC=CC=C5
Formula C31H33N5O4 M.Wt 539.62
Solubility Soluble in DMSO Storage Store at -20°C
Shipping Condition: Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Background

Nintedanib (BIBF 1120) is an indolinone-derived oral active, triple angiokinase inhibitor of vascular endothelial growth factor receptor (VEGFR)1-3, fibroblast growth factor receptor (FGFR)1-3 and platelet-derived growth factor receptor (PDGFR)α/β1. It has shown potent antiangiogenic activity at nanomolar (IC50, 20-100 nmol/L) by blocking these receptor-mediated signaling pathways1,2. Nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis as these receptors have been shown to be potentially involved in the pathogenesis of pulmonary fibrosis3,4. As a novel angiogenesis inhibitor, it is also being widely evaluated in different cancer models and has displayed significant anti-tumor activities by inhibiting tumor blood vessel formation5-7.

To further evaluate its antitumor effects on multiple tumors, Nintedanib is currently entering several clinical trials, including non-small cell lung cancer8, ovarian cancer6, colorectal cancer7, hepatocellular carcinoma9 and many other solid tumors. In addition, the possibilities of combining Nintedanib therapy with other treatments such as docetaxel10 and afatinib 11are being tested in different tumor models. The most common drug-related adverse events in patients were diarrhea, nausea, vomiting and lethargy7.

References:
[1]Hilberg, F. et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer research 68, 4774-4782, doi:10.1158/0008-5472.CAN-07-6307 (2008).[2]Roth, G. J. et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). Journal of medicinal chemistry 52, 4466-4480, doi:10.1021/jm900431g (2009).[3]Wollin, L., Maillet, I., Quesniaux, V., Holweg, A. & Ryffel, B. Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase Inhibitor Nintedanib in Experimental Models of Lung Fibrosis. The Journal of pharmacology and experimental therapeutics 349, 209-220, doi:10.1124/jpet.113.208223 (2014).[4]Antoniu, S. A. Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? Multidisciplinary respiratory medicine 7, 41, doi:10.1186/2049-6958-7-41 (2012).[5]Santos, E. S., Gomez, J. E. & Raez, L. E. Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor. Investigational new drugs 30, 1261-1269, doi:10.1007/s10637-011-9644-2 (2012).[6]Wei, X. W., Zhang, Z. R. & Wei, Y. Q. Anti-angiogenic drugs currently in Phase II clinical trials for gynecological cancer treatment. Expert opinion on investigational drugs 22, 1181-1192, doi:10.1517/13543784.2013.812071 (2013).[7]Mross, K. et al. Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 16, 311-319, doi:10.1158/1078-0432.CCR-09-0694 (2010).[8]Rolfo, C. et al. BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer. Expert opinion on investigational drugs 22, 1081-1088, doi:10.1517/13543784.2013.812630 (2013).[9]Tai, W. T. et al. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. Journal of hepatology, doi:10.1016/j.jhep.2014.03.017 (2014).[10]Reck, M. et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. The lancet oncology 15, 143-155, doi:10.1016/S1470-2045(13)70586-2 (2014).[11]Bouche, O. et al. Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer. Anticancer research 31, 2271-2281 (2011).