Dovitinib lactate hydrate

SKU: orb1300733

Description

Dovitinib lactate hydrate (TKI258) is a multi-targeted receptor tyrosine kinase (RTK) inhibitor with high potency against class III (FLT3, c-Kit), class IV (FGFR1/3), and class V (VEGFR1-4) receptors. It has been used in preclinical research, including in vitro cell-based assays and in vivo xenograft models, to study angiogenesis and oncogenic signaling in various cancers.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 915769-50-5
• MW: 482.51
• Purity: 99.82%
• Formula: C₂₄H₂₇FN₆O₄
• SMILES: O.CC(O)C(O)=O.CN1CCN(CC1)c1ccc2nc([nH]c2c1)-c1c(N)c2c(F)cccc2[nH]c1=O
• Target: PDGFR,FGFR,FLT,c-Kit,VEGFR
• Solubility: H2O:61 mg/mL (126.42 mM);Ethanol:1 mg/mL (2.07 mM);DMSO:13.89 mg/mL (28.79 mM)

Bioactivity

• Target IC50:
  PDGFRα:27 nM|PDGFRβ:210 nM|FGFR3:9 nM|FLT3:1 nM|c-Kit:2 nM|FGFR1:8 nM|VEGFR1:1 nM|VEGFR3:8 nM|VEGFR2:13 nM
• In Vivo:
  Dovitinib induces both cytostatic and cytotoxic responses in vivo resulting in regression of FGFR3-expressing tumors Dovitinib shows a dose- and exposure-dependent Inhibition of target receptor tyrosine kinases (RTKs) expressed in tumor xenografts. Dovitinib potently inhibits tumor growth of Six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFRβ/VEGFR2 signaling pathways. In an orthotopic model, Dovitinib potently inhibits Primary tumor growth and lung metastasis and significantly prolonged mouse survival. Administration of Dovitinib results in significant tumor growth Inhibition and tumor regressions, including large, established tumors (500-1,000 mm3).
• In Vitro:
  Dovitinib potently inhibit the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with an IC50 of 25 nM and inhibits proliferation of B9 cells expressing various activated FGFR3 mutants, showing minimal sensitivity differences with IC50 ranging from 70 to 90 nM. IL-6-dependent B9 cells containing vector only (B9-MINV cells) are resistant to Dovitinib at concentration up to 1 μM. Dovitinib inhibits proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of 90 nM (KMS11 and OPM2) and 550 nM, respectively It also inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity in FGFR3-expressing Primary mM cells, with BMSCs conferring modest resistance (44.6% growth Inhibition at 500 nM Dovitinib on stroma vs. 71.6% without BMSCs). In M-NFS-60 cells, Dovitinib has an EC50 of 220 nM. In SK-HEP1 cells, Dovitinib reduces cell number in a dose-dependent manner, induces G2/M phase arrest, inhibits anchorage-independent growth, and blocks bFGF-induced cell motility, with an IC50 of ~1.7 μM. It significantly reduces basal phosphorylation levels of FGFR-1, FRS2-α, and ERK1/2 but not Akt In both SK-HEP1 and 21-0208 cells and inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, and ERK1/2 but not Akt in 21-0208 cells.
• 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 concentration 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 evaluat 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.
• Disclaimer: For research use only

Alternative Names

Dovitinib (TKI258) Lactate, Dovitinib Lactate, Dovitinib lactate hydrate, Dovitinib lactate Hydrate, Cluster of differentiation antigen 135, CHIR-258 lactate, CD135, CD117, cKit, c-Kit, inhibit, multi-targeted, kinase, Platelet-derived growth factor receptor, PDGFRα, PDGFRβ, PDGFR, Inhibitor, FLT3, Fibroblast growth factor receptor, Fms like tyrosine kinase 3, FGFR, FGFR1, FGFR3, SCFR, tyrosine, TKI 258, TKI258, TKI-258, TKI258 lactate, Vascular endothelial growth factor receptor, VEGFR2, VEGFR1, VEGFR, VEGFR3, VEGFR3/FLT4

Compound Identifiers

PubChem CID

135611162