ATN-224
(Synonyms: 四硫钼酸二胆碱) 目录号 : GC18537
ATN-224是四硫代钼酸铵（tetrathiomolybdate, TM）的双胆碱盐，为超氧化物歧化酶抑制剂和高亲和力铜螯合剂，可抑制血液及内皮细胞中的CuZn超氧化物歧化酶1（SOD1）活性，从而发挥抗血管生成和抗肿瘤作用。
Cas No.:649749-10-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
ATN-224, the bis-choline salt of tetrathiomolybdate (TM), is a superoxide dismutase inhibitor and specific, high-affinity copper binder that suppresses CuZn superoxide dismutase 1 (SOD1) activity in blood and endothelial cells, leading to antiangiogenic and antitumour effects[1-3]. ATN-224 inhibited Fibroblast growth factor-2 (FGF-2)-induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in a dose-dependent (0, 0.625, 1.25, 2.5, 5, 10μM) and time-dependent (0, 1, 2, 4, 6, 8, 16, 24, 48h) manner with an IC50 between 1.25 and 2.5μM[4].
In vitro, treatment of WEHI7.2 and its variants, namely, hydrogen-peroxide-resistant 200R cells and Bcl-2-overexpressing Hb12 cells, with 0-10nM ATN-224 for 48h decreased the number of viable cells in a concentration-dependent manner, yielding EC50 values of 3.17±0.27, 5.84±0.34, and 5.25±0.32nM, respectively. Concurrently, ATN-224 markedly elevated caspase-3 activity and propidium iodide (PI) uptake in all three cell lines[5]. Treatment of SUDHL-10 cells with 32.71±2.04nM ATN-224 caused a significant drop in mitochondrial membrane potential (ΔΨm) within 12h and a pronounced reduction in Mcl-1 protein levels by 48h[6].
In vivo, in Matrigel plug model female BALB/c nude mice, 500µL 94µM ATN-224, delivered subcutaneously within the Matrigel plug significantly inhibited angiogenesis[4]. In nude mice bearing CAL27 squamous cell carcinoma (SCC) xenografts, daily oral gavage of 0.7mg ATN-224 combined with intratumoral Phosphate-Buffered Saline (PBS) or RAMBO on days 7 and 16 resulted in a significantly smaller average tumor volume in the RAMBO group by day 21 after ATN-224 treatment initiation[7].
References:
[1] Trapp V, Lee K, Doñate F, et al. Redox-related antimelanoma activity of ATN-224. Melanoma Res. 2009;19(6):350-360.
[2] Lowndes SA, Sheldon HV, Cai S, et al. Copper chelator ATN-224 inhibits endothelial function by multiple mechanisms. Microvasc Res. 2009;77(3):314-326.
[3] Doñate F, Juarez JC, Burnett ME, et al. Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224). Br J Cancer. 2008;98(4):776-783.
[4] Juarez JC, Betancourt O Jr, Pirie-Shepherd SR, et al. Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1. Clin Cancer Res. 2006;12(16):4974-4982.
[5] Lee K, Briehl MM, Mazar AP, et al. The copper chelator ATN-224 induces peroxynitrite-dependent cell death in hematological malignancies. Free Radic Biol Med. 2013;60:157-167.
[6] Lee K, Hart MR, Briehl MM, et al. The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B-cell lymphoma. Int J Oncol. 2014;45(1):439-447.
[7] Yoo JY, Yu JG, Kaka A, et al. ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma. Mol Ther Oncolytics. 2015;2:15008.
ATN-224是四硫代钼酸铵（tetrathiomolybdate, TM）的双胆碱盐，为超氧化物歧化酶抑制剂和高亲和力铜螯合剂，可抑制血液及内皮细胞中的CuZn超氧化物歧化酶1（SOD1）活性，从而发挥抗血管生成和抗肿瘤作用[1-3]。ATN-224以剂量（0、0.625、1.25、2.5、5、10μM）和时间（0、1、2、4、6、8、16、24、48h）依赖方式抑制成纤维细胞生长因子-2（FGF-2）诱导的细胞外信号调节激酶1/2（ERK1/2）磷酸化，其IC50介于1.25-2.5μM之间[4]。
在体外，0-10nM的ATN-224处理WEHI7.2及其衍生细胞（过氧化氢耐受的200R细胞和Bcl-2过表达的Hb12细胞）48h后，活细胞数呈浓度依赖性下降，EC50分别为3.17±0.27、5.84±0.34和5.25±0.32nM；同时，caspase-3活性与碘化丙啶（PI）摄取显著升高[5]。以32.71±2.04nM的ATN-224处理SUDHL-10细胞，12h后线粒体膜电位（ΔΨm）显著下降，48h后Mcl-1蛋白水平明显降低[6]。
在体内，在雌性BALB/c裸鼠Matrigel栓模型中，500μL 94μM的ATN-224皮下注射在Matriger塞内显著抑制血管生成[4]。在CAL27鳞状细胞癌（SCC）裸鼠移植瘤模型中，每日口服0.7mg的ATN-224，并于第7和第16天瘤内注射PBS或RAMBO，治疗开始后第21天RAMBO组的平均肿瘤体积显著小于对照组[7]。
| Cell experiment [1]: | |
Cell lines | Murine thymic lymphoma WEHI7.2 cells (include 200R and Hb12 cells) |
Preparation Method | The Murine thymic lymphoma WEHI7.2 variants include WEHI7.2 cells selected for resistance to hydrogen peroxide (200R) and WEHI7.2 cells overexpressing Bcl-2 (Hb12 cells). For 1 week before each experiment, 200R cells were cultured in medium without H2O2. The number of viable treated cells, relative to control cells, was measured after 48h of ATN-224 treatment in murine cell lines. Absorbance was read at 490nm using a plate reader. The MTS assay was used to determine the estimated EC50 for ATN-224. Viable cell number was also determined by propidium iodide, a membrane-impermeant dye that intercalates with DNA in dying cells, which was measured using a flow cytometer. Ten thousand cells were analyzed per sample. Numbers less than 5% different were considered within the error of the machine after calibration for this assay. |
Reaction Conditions | 0-10nM; 48h |
Applications | In the WEHI7.2 and WEHI7.2 variant cells, nanomolar concentrations of ATN-224 decreased the number of viable cells in a concentration-dependent manner. The EC50 values for the WEHI7.2, Hb12, and 200R cells were 3.17±0.27, 5.84±0.34, and 5.25±0.32nM, respectively. ATN-224 treatment in the WEHI7.2 and WEHI7.2 variant cells resulted in significant increases in caspase 3 activity and propidium iodide (PI) uptake. |
| Animal experiment [2]: | |
Animal models | Female BALB/c nude mice |
Preparation Method | Cold Matrigel (500μL) was mixed with 800ng/mL FGF-2 or 300ng/mL VEGF and heparin (50μg/mL). Negative control plugs did not contain the proangiogenic factors. The Matrigel mixture was injected s.c. into 4- to 8-week-old female BALB/c nude mice. In some experiments, either ATN-224 (94μmol/L) or water was added directly to the Matrigel plug in the treated and negative control groups, respectively. Animals were sacrificed, and the plugs were recovered 5 days after plug injection. The plugs were then minced and homogenized with a tissue homogenizer, and hemoglobin levels in the plugs were determined using Drabkin's solution. |
Dosage form | 500μL, 94μmol/L; injected s.c. |
Applications | ATN-224 significantly inhibited angiogenesis in the Matrigel plug model in mice, when added directly to the plug. |
References: | |
| Cas No. | 649749-10-0 | SDF | |
| 别名 | 四硫钼酸二胆碱 | ||
| 化学名 | 2-hydroxy-N,N,N-trimethyl-ethanaminium, tetrathioxomolybdate | ||
| Canonical SMILES | C[N+](C)(C)CCO.C[N+](C)(C)CCO.S=[Mo-2](=S)(=S)=S | ||
| 分子式 | C5H14NO.1/2MoS4 | 分子量 | 432.5 |
| 溶解度 | DMSO: 20 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3121 mL | 11.5607 mL | 23.1214 mL |
| 5 mM | 462.4 μL | 2.3121 mL | 4.6243 mL |
| 10 mM | 231.2 μL | 1.1561 mL | 2.3121 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet