Dovitinib lactate

SKU: orb1300069

Description

Dovitinib lactate (TKI-258) is a potent small molecule inhibitor targeting Fibroblast Growth Factor Receptor 3 (FGFR3) with an IC50 of 5 nM. It is widely used in preclinical research to investigate FGFR3-driven signaling pathways in vitro and has demonstrated antitumor activity in various in vivo cancer models, including bladder cancer and multiple myeloma.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 692737-80-7
• MW: 482.51
• Purity: >99.99% (May vary between batches)
• Formula: C₂₄H₂₇FN₆O₄
• SMILES: CC(O)C(O)=O.CN1CCN(CC1)c1ccc2nc([nH]c2c1)-c1c(N)c2c(F)cccc2[nH]c1=O
• Target: FGFR,c-Kit,FLT,VEGFR,PDGFR
• Solubility: DMSO:25 mg/mL (51.81 mM)

Bioactivity

• Target IC50:
  FGFR1:8 nM|c-Kit:2 nM|FGFR3:5 nM|PDGFRα:27 nM|FLT3:1 nM|PDGFRβ:210 nM|VEGFR1:1 nM|VEGFR2:13 nM|VEGFR3:8 nM
• In Vivo:
  In vivo, dovitinib potently inhibited tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFR-β/VEGFR-2 signaling pathways. Dovitinib also caused dephosphorylation of retinoblastoma, upregulation of p-histone H2A-X and p27, and downregulation of p-cdk-2 and cyclin B1, which resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. In an orthotopic model, dovitinib potently inhibited primary tumor growth and lung metastasis and significantly prolonged mouse survival.
• In Vitro:
  ALL cells were extremely sensitive to TKI258 treatment with a concentration for 50% inhibition of cell proliferation (IC50) values in the nanomolar range in vitro. By combination with mTOR inhibitor RAD001, a synergistic effect on cell death and cell proliferation was observed in these cells.Treatment of SK-HEP1 cells with dovitinib resulted in G2/M cell cycle arrest, inhibition of colony formation in soft agar and blockade of bFGF-induced cell migration. Dovitinib inhibited basal expression and FGF-induced phosphorylation of FGFR-1, FRS2-α and ERK1/2
• Cell Research:
  Determination of cell proliferation by 3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. Different leukemic cells were seeded into a 96-well plate at a density of 5×10^3 cells per well and exposed to different concentrations of TKI258, with or without RAD001, in culture medium. After incubation for indicated time points.Cell-cycle analysis:For cell-cycle analysis, cells were exposed to different concentrations of TKI258, with or without RAD001, in growth medium. After different culture durations, cells were harvested and fixed in 70% ethanol at 4°C for over 30 min. After incubation for indicated time points, DNA contents were stained.Apoptosis analysis:Cell apoptosis was detected by determining phosphatidylserine expression on the cell surface.
• Animal Research:
  21-0208 and SK-HEP1 cells as well as patient-derived HCC models were employed to study the antitumor effect of dovitinib. Changes of biomarkers relevant to FGFR/VEGFR/PDGFR pathways were determined by Western blotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, Fibroblast growth factor receptor, FGFR, FGFR3, Fms like tyrosine kinase 3, FLT3, Platelet-derived growth factor receptor, inhibit, Dovitinib, Dovitinib lactate, Dovitinib Lactate, cKit, c-Kit, Cluster of differentiation antigen 135, CD135, CHIR258, CHIR-258, CHIR258 Lactate, CHIR-258 Lactate, CHIR-258 lactate, CHIR 258 Lactate, CHIR 258, CD117, Vascular endothelial growth factor receptor, VEGFR, TKI 258, TKI 258 Lactate, TKI258, TKI-258, TKI258 Lactate, TKI-258 lactate, TKI-258 Lactate, PDGFR, SCFR

Compound Identifiers

PubChem CID

135431668