The target of SNS-314 is the Aurora kinase family (Aurora-A, Aurora-B, Aurora-C), acting as a pan-Aurora kinase inhibitor. It is an ATP-competitive inhibitor with potent and selective inhibitory activity against Aurora kinases. [1,2]

SNS-314 可抑制多种肿瘤细胞系的生长，包括 HeLa、PC-3、A2780、MDA-MB-231、H-1299 和 HT29。这些细胞系的 IC50 值范围从卵巢癌细胞中的 1.8 nM 到结肠癌细胞、A2780 和 HT29 中的 24 nM[2]。

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1. 抑制肿瘤细胞增殖：SNS-314可强效抑制多种肿瘤细胞系（包括HCT116、HT29、HeLa细胞）的增殖，其抑制效果与极光激酶活性的抑制程度相关[2]
2. 抑制组蛋白H3磷酸化：SNS-314能抑制肿瘤细胞中组蛋白H3的磷酸化（极光-B激酶活性的标志性指标），该抑制作用与极光激酶抑制诱导的细胞表型变化一致[2]
3. 影响细胞周期与细胞表型：SNS-314可破坏肿瘤细胞的细胞周期进程，增加细胞核含量和细胞体积，降低细胞活力并诱导细胞凋亡，这些表型均符合极光激酶被抑制的特征[1,2]
4. 诱导细胞凋亡：SNS-314可诱导肿瘤细胞凋亡，表现为处理后的细胞中caspase-3活性水平升高[2]

在 HCT116 人结肠癌异种移植模型中，50 和 100 mg/kg SNS-314 的治疗会导致组蛋白 H3 磷酸化的剂量依赖性抑制，这种抑制持续至少 10 小时。当按照一系列治疗方案（例如每周、每两周或五天停药九天）给药时，SNS-314 表现出剂量依赖性的显着肿瘤生长抑制作用[2]。

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1. 对HCT116人结肠癌异种移植模型的疗效：给荷HCT116异种移植瘤的裸鼠施用50 mg/kg和100 mg/kg剂量的SNS-314，可剂量依赖性抑制组蛋白H3磷酸化，且抑制效果至少持续10小时，证明其在体内能有效抑制极光-B激酶活性[2]
2. 肿瘤组织生物学变化：经SNS-314处理的HCT116移植瘤呈现强效且持续的生物学应答，包括磷酸化组蛋白H3水平降低、caspase-3表达增加，以及出现核体积增大的细胞[2]
3. 抑制肿瘤生长：SNS-314在HCT116异种移植模型中，经每周、每两周、“给药5天/停药9天”等多种给药方案处理后，均能剂量依赖性显著抑制肿瘤生长[1,2]
4. 给药灵活性：SNS-314在体内展现出给药灵活性，不同给药方案下均能维持抗肿瘤活性，提示其具备临床给药方案优化的潜力[2]

1. 极光激酶生化效价与选择性实验：采用重组Aurora-A、Aurora-B、Aurora-C激酶，评估SNS-314对各亚型的抑制活性。实验通过检测底物磷酸化水平来衡量激酶活性，以此评估SNS-314的ATP竞争性抑制作用。结果证实SNS-314是Aurora-A、Aurora-B、Aurora-C的强效、选择性抑制剂，对其他丝氨酸/苏氨酸激酶无显著抑制作用[2]

1. 肿瘤细胞增殖实验：体外培养多种肿瘤细胞系（HCT116、HT29、HeLa等），并给予不同浓度的SNS-314处理，通过标准细胞活力实验在设定时间内评估细胞增殖情况。结果显示SNS-314能强效抑制这些肿瘤细胞系的增殖，且抑制效果与SNS-314浓度相关[2]
2. 组蛋白H3磷酸化实验：体外用SNS-314处理肿瘤细胞，在不同时间点制备细胞裂解物，通过蛋白免疫印迹法（Western blot），利用组蛋白H3磷酸化特异性抗体检测磷酸化水平（极光-B激酶活性的读数）。实验证实SNS-314能剂量依赖性抑制组蛋白H3磷酸化[2]
3. 细胞周期与核表型分析实验：对SNS-314处理后的肿瘤细胞进行染色，通过流式细胞术分析细胞周期时相分布，借助显微镜观察细胞核大小和含量，评估细胞周期进程和核形态变化。结果显示SNS-314破坏正常细胞周期进程，导致细胞核含量和细胞体积增加，与极光激酶抑制的特征一致[2]
4. 细胞凋亡实验：通过检测caspase-3活性和细胞活力，评估SNS-314处理后肿瘤细胞的凋亡情况。利用特异性底物或抗体检测caspase-3活性，采用标准活力染料评估细胞存活率。结果证实SNS-314可诱导肿瘤细胞凋亡，表现为caspase-3活性升高、细胞存活率降低[2]

Dissolved in 20% Captisol R.; 42 mg/kg; i.p. injection
HCT116 cells are injected s.c. into the right flank of nu/nu mice

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1. HCT116 human colon cancer xenograft model: Female nude mice were implanted with HCT116 human colon cancer cells to establish xenograft tumors. Once tumors reached a measurable size, mice were randomized into treatment groups and administered SNS-314 at doses of 50 mg/kg and 100 mg/kg via an unspecified route (not described in the literature). The dosing schedules included weekly, bi-weekly, and 5 days on/9 days off regimens. Tumor volumes were measured regularly to evaluate tumor growth inhibition. At the end of the treatment period, tumors were harvested to analyze biological markers (phosphorylated histone H3, caspase-3, nuclear size) [2]
2. Pharmacodynamic assessment in xenograft models: Mice treated with SNS-314 were euthanized at different time points (up to 10 hours post-administration) to collect tumor tissues and blood samples (no blood sample analysis described). Tumor lysates were prepared to measure histone H3 phosphorylation levels, assessing the duration of Aurora-B inhibition in vivo [2]

[1]. Discovery of a potent and selective aurora kinase inhibitor. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4.

[2]. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.

1-(3-chlorophenyl)-3-[5-[2-(4-thieno[3,2-d]pyrimidinylamino)ethyl]-2-thiazolyl]urea is a member of ureas.
SNS-314 is a potent and selective inhibitor of Aurora kinases A, B, and C. Proliferating cells treated with SNS-314 bypass the mitotic spindle checkpoint and fail to undergo cytokinesis, leading to multiple rounds of endoreduplication and eventually cell death. SNS-314 inhibits tumor growth in a variety of preclinical models, and it is now being tested in single agent Phase 1 studies in patients with advanced solid tumours.
Aurora Kinase Inhibitor SNS-314 is a synthetic small molecule Aurora kinase (AK) inhibitor with potential antineoplastic activity. Aurora kinase inhibitor SNS-314 selectively binds to and inhibits AKs A and B, which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress AKs. AKs are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis.

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Drug Indication
Investigated for use/treatment in solid tumors.

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Mechanism of Action
The process of cell division, or mitosis, plays a critical role in the uncontrolled proliferation that is a hallmark of cancer. During mitosis, a cell aligns duplicate copies of its DNA along a mitotic spindle and subdivides itself through a process called cytokinesis, creating two identical daughter cells. This process is often poorly regulated in cancer, leading to rapid proliferation and tissue growth. Aurora kinases (A, B, and C) play important, though differentiated, roles in mitosis. Aurora A controls the formation of the spindle assembly, while Aurora B ensures that the DNA is appropriately aligned and that cytokinesis proceeds successfully. Less is known about Aurora C, though it is thought to serve many of the same functions as Aurora B. Elevated expression of Aurora A has been detected in a high percentage of colon, breast, ovarian, gastric, and pancreatic tumors. Aurora B and C are also expressed at high levels in primary tumors. Given the central roles of all three Aurora kinases in regulating mitosis and the association between their overexpression and tumorigenesis, they are being evaluated as potential targets in cancer therapy. SNS-314 is a potent inhibitor of all 3 Aurora kinases. Cells treated with SNS-314 make additional copies of their DNA, but are unable to create functional spindle assemblies or replicate. As a result, these cells are unable to progress, and ultimately die by a variety of mechanisms. Since most normal cells are not undergoing mitosis in their normal settings, SNS-314 is expected to affect only highly proliferating tissues, particularly tumor tissues. SNS-314 is being tested in a Phase 1 trial in patients with advanced solid tumor malignancies.

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1. SNS-314 (compound 21 in literature [1]) is a novel small-molecule pan-Aurora kinase inhibitor developed as an anti-cancer therapeutic agent. It is an ATP-competitive inhibitor with potent and selective activity against Aurora-A, Aurora-B, and Aurora-C kinases [1,2]
2. Aurora kinases (Aurora-A, Aurora-B, Aurora-C) play a key role in the orderly progression of cells through mitosis. Elevated expression levels of Aurora kinases are detected in a high percentage of melanoma, colon, breast, ovarian, gastric, and pancreatic tumors, making them attractive targets for anti-cancer therapy [2]
3. SNS-314 induces phenotypes consistent with Aurora kinase inhibition in tumor cells (inhibition of proliferation, disruption of cell cycle, induction of apoptosis) and exhibits significant anti-tumor activity in pre-clinical in vivo tumor models with dosing flexibility, supporting its potential for the treatment of diverse human malignancies [1,2]
4. Key structure-activity relationship (SAR) and critical binding elements of SNS-314 and its analogues were investigated, leading to the identification of SNS-314 as a potent and selective Aurora kinase inhibitor with pre-clinical anti-tumor activity [1]

C18H15CLN6OS2

430.93

430.043

1057249-41-8

SNS-314 mesylate;1146618-41-8

24995524

Typically exists as solid at room temperature

1.6±0.1 g/cm3

1.815

5.36

155.03

3

7

6

28

532

0

ClC1=CC=CC(=C1)NC(NC1=NC=C(CCNC2=C3C(C=CS3)=NC=N2)S1)=O

FAYAUAZLLLJJGH-UHFFFAOYSA-N

InChI=1S/C18H15ClN6OS2/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/h1-3,5,7-10H,4,6H2,(H,20,22,23)(H2,21,24,25,26)

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

SNS314; SNS-314; SNS 314

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
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示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
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注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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