SNS-314 Mesylate

Catalog No.S8699

SNS-314 Mesylate Chemical Structure

Molecular Weight(MW): 430.93

SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively and less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2.

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Biological Activity

Description SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively and less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2.
Targets
Aurora C [1]
(Cell-free assay)
Aurora A [1]
(Cell-free assay)
Aurora B [1]
(Cell-free assay)
3 nM 9 nM 31 nM
In vitro

In HCT116 colorectal carcinoma cell line, with intact or depleted p53 protein levels, SNS-314 Mesylate shows enhanced efficacy when administered sequentially with other standard chemotherapeutic agents and the most profound synergies are identified for agents that activate the spindle assembly checkpoint, e.g., docetaxel and vincristine[2]. A recent study shows that SNS-314 Mesylate shows potent antiproliferative activity in HCT116 cells and inhibits soft agar colony formation[3].

In vivo The sequential treatment with SNS-314 Mesylate followed by docetaxel 24 hours later produces a significant 72.5% tumor growth inhibition of HCT116 xenografts, while docetaxel and SNS-314 Mesylate as single agents produce no significant inhibition of HCT116 tumor growth[2]. In the HCT116 human colon cancer xenograft model, administration of 50 and 100 mg/kg SNS-314 Mesylate results a dose-dependent inhibition of histone H3 phosphorylation, indicating effective Aurora-B inhibition in vivo. In addition, HCT116 tumors from animals treated with SNS-314 Mesylate exhibits potent and sustained responses including reduction of phosphorylated histone H3 levels, increased caspase-3 and appearance of increased nuclear size[3].

Protocol

Cell Research:

[2]

+ Expand
  • Cell lines: HCT116 SCR and HCT116 p53 RNAi cells
  • Concentrations: ~125 nM
  • Incubation Time: 48 h
  • Method:

    Viability is measured using the CellTiter-Blue cell viability assay. Cells are treated as described above, although with a 5-day incubation period. Cytotoxicity is determined by measuring intracellular ATP using the CellTiter-Glo Luminescence Cell Viability Assay. Cells are seeded in white 96-well tissue culture plates at a density of 1.5-2 × 103 cells/well, and a serial dilution of SNS-314 is dosed in combination with fixed concentrations of either docetaxel or vincristine for a total of 72 hours. Viability is determined as the ratio between the ATP in treated cells versus control cells. Apoptosis is measured using the caspase-Glo 3/7 system. Cells are plated in white 96-well plates as described above and treated first with SNS-314 for 24 hours, washed with 200 μL of 1× PBS, and fresh medium is added with the second agent for 24 hours.


    (Only for Reference)
Animal Research:

[2]

+ Expand
  • Animal Models: HCT116 cells are injected s.c. into the right flank of nu/nu mice
  • Formulation: 20% Captisol R
  • Dosages: ≤42.5 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 86 mg/mL warmed (199.56 mM)
Ethanol 1 mg/mL warmed (2.32 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 430.93
Formula

C18H15ClN6OS2.CH4O3S

CAS No. 1057249-41-8
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Aurora Kinase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID