SKU: N065

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Description
Nintedanib is an indolinone derivative and small molecule tyrosine-kinase inhibitor, inhibiting endothelial growth factor activity in enzymatic assays.    It targets vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR) α and β, which may result cell apoptosis, a reduction in tumor vasculature; and the inhibition of tumor cell proliferation and migration.  This agent also inhibits some Src family of tyrosine kinases, including Src, Lck, Lyn, and FLT-3.

    CAS Number

    656247-17-5

    Molecular Formula

    C31H33N5O4

    Molecular Weight

    539.63

    Mechanism of Action

    Nintedanib binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain . Nintedanib binds to and blocks the activation of cell receptors involved in blood vessel formation (angiogenesis) and reshaping. It inhibits cell proliferation in 3 cell types: endothelial cells, pericytes, and smooth muscle cells, resulting in apoptosis. The compound blocks the intracellular signalling needed for the proliferation, migration and transformation of fibroblasts.

    Storage Conditions

    -20C

Applications

    Cancer Applications

    Nintedanib exerts its anti-cancer effect by binding to and blocking the activation of cell receptors involved in tumor blood vessel formation and reshaping,

    Eukaryotic Cell Culture Applications

    In vitro biochemical signaling pathway modulation studies found a distinct feature in cell culture is sustained pathway inhibition (up to 32 hrs after 1 hr of exposure). Tumor cell lines FaDu, Caki-1, HT-29, SKOV-3, H460, Calu-6, PAC-12, and the rat glioma cell line GS-9L were used in this study. Treatment of VEGF-stimulated human endothelial cells from umbilical veins and human skin microvessels with the compound resulted in inhibition of cell proliferation and apoptosis (EC50, <10 nmol/L). Pericytes, important for vessel maturation and stabilization, are known to express PDGFRs, and Nintedanib inhibited proliferation of PDGF-BB–stimulated BRPs (EC50 79 nmol/L).(Hilberg et al, 2008)

Specifications

    Source

    synthetic

References

    References

    Hilberg F et al (2008) BIBF 1120: Triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 68(12):4774-4782. PMID 18559524 Lehtonen, ST et al (2016) Pirfenidone and nintedanib modulate properties of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis. Resp. Res.17(14) DOI 10.1186. PMID 26846335

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