Dovitinib

SKU: orb1300899

Description

Dovitinib is an orally bioavailable small molecule that inhibits multiple receptor tyrosine kinases (RTKs). It has demonstrated anti-tumor activity in preclinical research, including in vitro cell proliferation assays and in vivo xenograft models, supporting its investigation in oncology.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 405169-16-6
• MW: 392.43
• Purity: 99.92% (May vary between batches)
• Formula: C₂₁H₂₁FN₆O
• SMILES: CN1CCN(CC1)c1ccc2nc([nH]c2c1)-c1c(N)c2c(F)cccc2[nH]c1=O
• Target: FLT,FGFR,c-Fms,c-Kit,PDGFR,VEGFR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.55 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:15.63 mg/mL (39.83 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  CSF1R:36 nM|VEGFR1-4 (Class V):8-13 nM|c-Kit:2 nM|FGFR1:8 nM|PDGFRα:210 nM|FGFR3:9 nM|PDGFRβ:27 nM|FLT3:1 nM
• In Vivo:
  METHODS: Dovitinib (CHIR-258) (10, 30, 60 mg/kg, orally, once a day, 21 days) was used to treat tumor xenograft model mice, and the growth of tumors in vivo was observed. RESULTS Significant anti-tumor effects were observed in all three dovitinib dose groups. The minimum effective dose was 10 mg/kg. The growth inhibition in the 10 mg/kg, 30 mg/kg and 60 mg/kg treatment groups was 48% respectively. , 78.5% and 94%.
• In Vitro:
  METHODS: FGFR3 cell lines (KMS11, KMS18, OPM2, H929) and FGFR3 cell lines were treated with Dovitinib (CHIR-258) (12.5, 25, 50, 100, 200, 300, 400 nM, 48 hours), and cell viability was detected by MTT. RESULTS Dovitinib inhibited the proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 values ​​of 90 nM (KMS11 and OPM2) and 550 nM, respectively.
• Cell Research:
  Cell viability is assessed by 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance. Cells are seeded in 96-well plates at a density of 5 × 103 (B9 cells) or 2 × 104 (MM cell lines) cells per well. Cells are incubated with 30 ng/mL aFGF and 100 μg/mL heparin or 1% IL-6 where indicated and increasing concentrations of Dovitinib. For each concentration of Dovitinib, 10 μL aliquots of drug or DMSO diluted in culture medium is added. For drug combination studies, cells are incubated with 0.5 μM dexamethasone, 100 nM Dovitinib, or both simultaneously where indicated. To evaluate the effect of Dovitinib on growth of MM cells adherent to BMSCs, 104 KMS11 cells are cultured on BMSC-coated 96-well plates in the presence or absence of Dovitinib. Plates are incubated for 48 to 96 hours. For assessment of macrophage colony-stimulating factor (M-CSF)-mediated growth, 5 × 103 M-NFS-60 cells/well are incubated with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF). After 72 hours cell viability is determined using Cell Titer-Glo Assay. Each experimental condition is performed in triplicate. (Only for Reference)

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

colony stimulating factor 1 receptor, cKit, c-Kit, CD117, CD135, Cluster of differentiation antigen 135, CHIR 258, CHIR258, CHIR-258, c-Fms, Dovitinib, CSF1R, CSF-1R, CSF-1 receptor, KMS11, KMS18, inhibit, orally, OPM2, Inhibitor, FLT3, Fms like tyrosine kinase 3, Fibroblast growth factor receptor, FGFR, FGFR3, FGFR1, RTK, SCFR, TKI 258, TKI258, TKI-258, Platelet-derived growth factor receptor, PDGFR, Vascular endothelial growth factor receptor, VEGFR, VEGFR3/FLT4

Compound Identifiers

PubChem CID

135398510