SNS-314

製品コードS1154 バッチS115401

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₁₅ClN₆OS₂
	分子量	430.93	CAS No.	1057249-41-8
Solubility (25°C)*	体外	DMSO	105 mg/mL (243.65 mM)
		Water	6 mg/mL (13.92 mM)
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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. It is less potent to Trk A/B, Flt4, Fms, Axl, c-Raf and DDR2. Phase 1.
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]

プロトコル(参考用のみ)

キナーゼアッセイ	Aurora-A Kinase Assay
キナーゼアッセイ	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
細胞アッセイ	細胞株	HCT116 SCR and HCT116 p53 RNAi cells
	濃度	~125 nM
	反応時間	48 hours
	実験の流れ	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.
動物実験	動物モデル	HCT116 cells are injected s.c. into the right flank of nu/nu mice.
	投薬量	≤42.5 mg/kg
	投与方法	Administered via i.p.

参考

カスタマーフィードバック

: Data from [Data independently produced by Exp Cell Res, 2012, 318(4), 336-49]

: Data independently produced by , , Dr. Zhang of Tianjin Medical University

: Data from [Data independently produced by , , Oncotarget, 2017, 8(17):27953-27965]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

DELs enable the development of BRET probes for target engagement studies in cells [ Cell Chem Biol, 2023, 30(8):987-998.e24]	PubMed: 37490918
The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and Aurora kinases [ Res Sq, 2023, rs.3.rs-2570204]	PubMed: 36865133
Concomitant targeting of FLT3 and BTK overcomes FLT3 inhibitor resistance in acute myeloid leukemia through inhibition of autophagy [ Haematologica, 2022, 10.3324/haematol.2022.280884]	PubMed: 36226489
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2021, 13(6)1205]	PubMed: 33801977
Intratumoural Heterogeneity Underlies Distinct Therapy Responses and Treatment Resistance in Glioblastoma. [ Cancers (Basel), 2019, 11(2)]	PubMed: 30736342
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370]	PubMed: 30702467
Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma. [Liu F, et al. Oncotarget, 2017, 8(17):27953-27965]	PubMed: 28427193
The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line [Wang J, et al. Invest New Drugs, 2016, 10.1007/s10637-016-0358-3]	PubMed: 27177645
Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents [Jayanthan A, et al. PLoS One, 2014, 9(7):e102741]	PubMed: 25048812
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res, 2013, 73(20):6310-22]	PubMed: 24067506

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。