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SNS-314 Aurora Kinase inhibitor

Cat.No.S1154

SNS-314 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. It is less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. Phase 1.
SNS-314 Aurora Kinase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 430.93

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Quality Control

Batch: Purity: 99.07%
99.07

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (232.05 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 430.93 Formula

C18H15ClN6OS2

 Storage (From the date of receipt)
CAS No. 1057249-41-8 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC(=CC(=C1)Cl)NC(=O)NC2=NC=C(S2)CCNC3=NC=NC4=C3SC=C4

Mechanism of Action

Targets/IC50/Ki
Aurora C
3 nM
Aurora A
9 nM
Aurora B
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. A recent study shows that this compound shows potent antiproliferative activity in HCT116 cells and inhibits soft agar colony formation.

Kinase Assay
Aurora-A Kinase Assay
Humanized mouse Aurora A (amino acids 107-403) is expressed in E. coli as described previously. For IC50 assays, this compound is 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). This chemical is 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 this 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
In vivo

The sequential treatment with SNS-314 Mesylate 24 hours later produces a significant 72.5% tumor growth inhibition of HCT116 xenografts, while this compound 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 this chemical results a dose-dependent inhibition of histone H3 phosphorylation, indicating effective Aurora-B inhibition in vivo. In addition, HCT116 tumors from animals treated with this agent exhibits potent and sustained responses including reduction of phosphorylated histone H3 levels, increased caspase-3 and appearance of increased nuclear size.

References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00519662 Completed
Advanced Solid Tumors
Sunesis Pharmaceuticals
 August 2007 Phase 1

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