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    SNS-314 Mesylate
    SNS-314 Mesylate

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0367
    CAS #: 1146618-41-8Purity ≥98%

    Description: SNS-314 mesylate, the mesylate salt of SNS314, is a pan-Aurora kinase inhibitor with potential antineoplastic activity. It inhibits Aurora A/B/C with IC50s of 9 nM, 31 nM, and 3 nM, respectively. SNS 314 exhibits excellent antiproliferative activity and high in vivo antitumor efficacy.

    References: Mol Cancer Ther. 2009 Apr;8(4):930-9; Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.

    Related CAS: 1146618-41-8 (mesylate); 1057249-41-8 (free base)

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    Molecular Weight (MW)527.04
    CAS No.1146618-41-8 (mesylate); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 105 mg/mL (199.2 mM)
    Water: 6 mg/mL (11.4 mM)
    Ethanol: <1 mg/mL
    Solubility (In vivo)15% Captisol: ~6 mg/mL

    SNS314; SNS 314; SNS-314; SNS-314 mesylate

    Chemical Name: N-(3-Chlorophenyl)-N'-[5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-2-thiazolyl]urea mesylate


    InChi Code: InChI=1S/C18H15ClN6OS2.CH4O3S/c19-11-2-1-3-12(8-11)24-17(26)25-18-21-9-13(28-18)4-6-20-16-15-14(5-7-27-15)22-10-23-16;1-5(2,3)4/h1-3,5,7-10H,4,6H2,(H,20,22,23)(H2,21,24,25,26);1H3,(H,2,3,4)

    SMILES Code: O=C(NC1=NC=C(CCNC2=C3C(C=CS3)=NC=N2)S1)NC4=CC=CC(Cl)=C4.OS(=O)(C)=O 

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    In Vitro

    In vitro activity: 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. A recent study shows that SNS-314 Mesylate shows potent antiproliferative activity in HCT116 cells and inhibits soft agar colony formation.

    Kinase Assay: Humanized mouse Aurora A (amino acids 107-403) is expressed in E. coli as described previously. For IC50 assays, compounds are titrated three-fold in DMSO and diluted 12.5-fold into assay buffer (10 mM Tris HCl pH 7.2, 10 mM MgCl2, 0.05% NaN3, 0.01% Tween-20, and 0.1% BSA). Compounds are then diluted 4-fold into assay buffer containing Aurora A and FAM-PKAtide at final concentrations of 2 nM and 50 nM, respectively. The kinase reaction is initiated by adding ATP in assay buffer at a final concentration of 10 mM and incubated at 21 °C for 25 minutes. As a positive control, DMSO is added instead of compound and as a negative control assay buffer is added instead of Aurora A. Both control reactions are conducted in triplicate. To detect phosphorylated PKAtide, the kinase reaction is combined with Progressive Binding Solution (1:400 Progressive Binding Reagent, 1 × Buffer A, Molecular Devices) in a 1:3 ratio. The mixture is incubated for 30 minutes at 21 °C and the plate is scanned on an Analyst AD with excitation at 485 nm and emission at 530 nm. The percent relative enzymatic activity is calculated by normalizing the mP value for each well to the average positive control. Relative enzymatic activity values are plotted as a function of the logarithm of compound concentration and IC50 values are generated in GraphPad Prism software using a sigmoidal dose-response curve-fit. IC50's are calculated as the concentration of compound at which enzymatic activity.

    Cell Assay: 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 (HCT116 SCR and HCT116 p53 RNAi 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.

    In VivoThe 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. 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.
    Animal modelHCT116 cells are injected s.c. into the right flank of nu/nu mice
    Formulation & DosageDissolved in 20% Captisol R.; 42 mg/kg; i.p. injection

    Mol Cancer Ther. 2009 Apr;8(4):930-9; Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    SNS-314 Mesylate

    CI50 screening process of SNS-314 with cytotoxic anticancer agents.  2009 Apr;8(4):930-9.

    SNS-314 Mesylate

    SNS-314 combined with spindle toxins vincristine (VIN) or docetaxel (DTX) compromises the spindle checkpoint.  2009 Apr;8(4):930-9.

    SNS-314 Mesylate

    Effects of SNS-314 combinations with docetaxel (DTX) or vincristine (VIN) under a sequential administration schedule.  2009 Apr;8(4):930-9.

    SNS-314 Mesylate

    Combination of SNS-314 with spindle toxins results in synergistic inhibition of cell growth.  2009 Apr;8(4):930-9.

    SNS-314 Mesylate

    Sequential SNS-314/docetaxel dosing results in significant antitumor activity.  2009 Apr;8(4):930-9.

    SNS-314 Mesylate

    SNS-314 demonstrates significant and prolonged anti-tumor activity using flexible dosing schedules in HCT116 colon cancer xenografts.   2010 Mar;65(4):707-17.


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