Dovitinib Dilactic acid (TKI258 Dilactic acid)

Dovitinib (TKI258, CHIR-258) is a multitargeted tyrosine kinase inhibitor of FLT3 and c-KIT with IC50 of 1 nM and 2 nM, respectively.

Catalog No.S2769
5 5 4 Reviews 4 Product Citations
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Dovitinib Dilactic acid (TKI258 Dilactic acid) Chemical Structure
Molecular Weight: 572.59

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

Related Compound Libraries

Dovitinib Dilactic acid (TKI258 Dilactic acid) is available in the following compound libraries:

Product Information

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Product Description

Biological Activity

Dovitinib Dilactic acid (TKI258 Dilactic acid) is a highly potent, novel multitargeted growth factor receptor kinase inhibitor with IC50 of 1, 2, 10, 8, 27, 36 nM for FLT3, c-KIT, VEGFR1/2/3, PDGFRß and CSF-1R, respectively. It shows both antitumor and antiangiogenic activities in vivo. [1] It potently inhibits FGFR3 with an inhibitory concentration of 50% (IC50) of 5 nM in in vitro kinase assays and selectively inhibited the growth of B9 cells and human myeloma cell lines expressing wild-type (WT) or activated mutant FGFR3. Antiproliferative activity of Dovitinib Dilactic acid (TKI258 Dilactic acid) against MV4;11 was ~24-fold greater compared with RS4;11, indicating more potent inhibition against cells with constitutively activated FLT3 ITD. [2][3]

Chemical Information

Download Dovitinib Dilactic acid (TKI258 Dilactic acid) SDF
Molecular Weight (MW) 572.59
Formula

C21H21FN6O.2C3H6O3

CAS No. 852433-84-2, 405169-16-6 (free base)
Synonyms CHIR-258 Dilactic acid
Solubility (25°C)
  • DMSO 90 mg/mL
  • Water 70 mg/mL
  • Ethanol <1 mg/mL
Storage 2 years -20°CPowder
2 weeks4°Cin DMSO
6 months-80°Cin DMSO
Chemical Name Propanoic acid, 2-hydroxy-, compd. with 4-amino-5-fluoro-3-[6-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone

Research Area

Customer Reviews (4)


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Rating
Source Brit J Cancer , 2010, 104, 75-82. Dovitinib Dilactic acid (TKI258 Dilactic acid) purchased from Selleck
Method Western blotting, immunoprecipitation
Cell Lines RT112 cells
Concentrations 500 nM
Incubation Time 1 h
Results RT112 cells show constitutive activation of FGFR3 and were used to assess the effects of PD173074, SU5402 and TKI-258 on FGFR3 phosphorylation and downstream signalling (Figure B and C). A time-course of treatment with PD173074 showed a rapid and sustained inactivation of FGFR3 (Figure B). After 2 h of treatment, TKI-258 and other inhibitors all showed profound inhibition of FGFR3 phosphorylation. Recently, we have shown that FGFR3 activates the MAPK pathway in normal urothelial cells.

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Rating
Source haematologica, 2011, 96, 922-926. Dovitinib Dilactic acid (TKI258 Dilactic acid) purchased from Selleck
Method Western blot, Apoptotic assay
Cell Lines Ba/F3 cells
Concentrations 0-10000 nM
Incubation Time 48 h
Results CUX1-FGFR1-expressing Ba/F3 cells displayed IL-3 independent proliferation (Figure A). Treatment of the CUX1-FGFR1-expressing Ba/F3 cells with the kinase inhibitor TKI258 significantly inhibited cell growth with an IC 50 of 489 nM (Figure B). Westernblot analysis demonstrated a corresponding decrease in CUX1-FGFR1 phosphorylation with increasing doses of TKI258, while protein expression was unaffected (Figure C).Furthermore, using an Annexin-V/propidium iodide-based apoptosis assay, we could show that 48 h exposure to TKI258 induced apoptosis followed by cell death in CUX1-FGFR1-expressing Ba/F3 cells. Massive apoptosis/necrosis was recorded at 500 nM of TKI258 (Figure D).

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Rating
Source AACR, 2011, Dovitinib Dilactic acid (TKI258 Dilactic acid) purchased from Selleck
Method Cell viability assay
Cell Lines Ba/F3 cells
Concentrations 0-1000 nM
Incubation Time
Results Dovitinib inhibited the survival of Ba/F3 cell lines expressing the recombinant TEL/kinase domain fusion protein for FGFR1-4 in a dose-dependent manner.

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Rating
Source Brit J Cancer , 2010, 104, 75-82. Dovitinib Dilactic acid (TKI258 Dilactic acid) purchased from Selleck
Method Cell cycle and apoptosis analysis
Cell Lines RT112/RT4/SW780/MGH-U3/97-7 cell lines
Concentrations 500 nM
Incubation Time 24 h
Results A significant increase in the proportion of cells in G1 accompanied by a decrease in S and G2 /M phases was observed in PD173074- and TKI-258-treated RT112, RT4, MGH-U3 and 97-7 cells after 24-h exposure.

Product Citations (4)

  • The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11). [Wasag B, et al. Haematolog 2011;96(6), 922-926]

    PubMed: 21330321
  • Ponatinib (AP24534), a potent pan-FGFR inhibitor with activity in multiple FGFR-driven cancer models with distinct mechanisms of activation. [Gozgit JM, et al. Mol Cancer Ther 2011;10, 1028-1035]

    PubMed: 22238366
  • Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo. [Lamont FR, et al. Brit J Cancer 2010;104(1), 75-82]

    PubMed: 21119661
  • Evaluation of tyrosine receptor kinases in the interactions of head and neck squamous cell carcinoma cells and fibroblasts. [Sweeny L, et al. Oral Oncol 2012;48(12):1242-9]

    PubMed: 22795534

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