Nintedanib

SKU: orb1307463

Description

Nintedanib

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 656247-17-5
• MW: 539.62
• Purity: 99.92%
• Formula: C₃₁H₃₃N₅O₄
• SMILES: COC(c1cc2c(/C(C(N2)=O)=C(c3ccccc3)/Nc4ccc(N(C(CN5CCN(CC5)C)=O)C)cc4)cc1)=O
• Target: PDGFR,VEGFR,FGFR,FLT,Src
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:0.6 mg/mL (1.11 mM);Ethanol:3 mg/mL (5.56 mM);DMSO:13.1 mg/mL (24.28 mM)

Bioactivity

• Target IC50:
  VEGFR2:13 nM (cell free)|VEGFR3:13 nM (cell free)|VEGFR1:34 nM (cell free)|FGFR2:37 nM (cell free)|FGFR3:108 nM|PDGFRα:59 nM (cell free)|PDGFRβ:65 nM|FGFR1:69 nM (cell free)
• In Vivo:
  METHODS: To tes the antitumor activity in vivo Nintedanib (10-100 mg/kg) was administered by gavage to athymic nMRI-nu/nu mice bearin the human head and neck s All cell carcinoma tumor FaDu o the human renal carcinoma tumor Caki-1 once daily for 23-35 days. Results: Nintedanib inhibited tumor growth in FaDu and Caki-1. METHODS: To tes the antitumor activity in vivo Nintedanib (40 mg/kg) and TFTD (150 mg/kg) were administered intraperitoneally to BALB/c nu/nu mice bearing tumors of DLD-1, DLD-1/5-FU, HT-29, or HCT116 twice daily for two weeks. Results: At day 15, Nintedanib and TFTD monotherapy resulted in a significant reduction in tumor growth in vivo the combination therapy exhibited greater anti-tumor activity tha the two monotherapies.
• In Vitro:
  METHODS: Human nasopharyngeal carcinoma cells CNE-2, HNE-1 and HONE-1 were treated with Nintedanib (0.078-10 µM) for 72 h, and cell viability was measured by CCK8 assay. Results: Nintedanib significantly inhibite the growth of CNE-2, HNE-1 and HONE-1 cell lines in a dose-dependent manner with IC50 Values of 4.16 µM, 5.62 µM and 6.32 µM, respectively METHODS: Human endothelial cells HUVEC, smooth musclee cells HUASMC and bovine pericytes were treated with Nintedanib (0.03-1 µM) for 2 h, an the expression levels of target proteins were detected by Western Blot. Results: Nintedanib inhibited li and-dependent phosphorylation of MAPK and Akt in HUVEC, HUASMC and bovine pericytes.
• Cell Research:
  HUVEC, HUASMC, and BRP were cultured as described above. Two hours befor the addition of li ands, BIBF 1120 was added to the cultures. Cell lysates were generated according to s andard protocols. Western blotting was done using s andard SDS-PAGE methods, loading 50 to 75 μg of protein per lane, with detection by enhanced chemiluminescence. Total and phosphorylated mitogen-activated protein kinase (MAPK) was analyzed using monoclonal antibodies M3807 and M8159. Total Akt was detected usin the polyclonal antibody and phosphorylated Akt (Ser473) was analyzed wit the monoclonal antibody. Cleaved caspase-3 was detected wit the monoclonal antibody.
• Animal Research:
  Five-week-old to 6-wk-old athymic nMRI-nu/nu f Male mice (21–31 g) were purchased from Harlan. After acclimatization, mice were inoculated with 1 to 5 × 10^6 (in 100 μL) FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 cells s.c. int the right flank o the animal. F344 Fischer rats after acclimatization were injected with 5 × 10^6 (in 100 μL) GS-9L cells s.c. int the right flank o the animal. For pharmacokinetic analysis, blood was isolated at indicated time points fro the retroorbital plexus of mice and plasma was analyzed using high-performance liquid chromatography-mass spectrometry methodology.

Storage & Handling

• Storage: keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

PDGFRα, PDGFRβ, PDGFR, Platelet-derived growth factor receptor, Vascular endothelial growth factor receptor, VEGFR3, VEGFR1, VEGFR2, VEGFR, BIBF 1120, BIBF1120, BIBF-1120, Intedanib, Inhibitor, Lck, FGFR, FGFR1, FGFR2, FGFR3, Fibroblast growth factor receptor, FLT3, Nintedanib, inhibit

Compound Identifiers

PubChem CID

135423438