TAS4464
目录号 : GC37742
TAS4464是一种高效且选择性的NEDD8激活酶（NAE）抑制剂，IC50为0.955nM。
Cas No.:1848959-10-3
Sample solution is provided at 25 µL, 10mM.
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TAS4464 is a highly potent and selective inhibitor of NEDD8-activating enzyme (NAE), with an IC50 of 0.955nM. TAS4464 exhibits superior antitumor activity with prolonged target inhibition[1]. TAS4464 is commonly used in the study of acute myeloid leukemia[2] and multiple myeloma[3].
TAS4464 (0.1μM; 0, 8, and 24h) significantly induced apoptosis in acute myeloid leukemia HL-60 cells[2]. TAS4464 (0.3-1000nM, 72h) inhibits cell growth and induces apoptotic or mitotic cell death in multiple myeloma cell lines[4].
TAS4464 (50 or 100mg/kg, twice a week; 3 weeks; i.v.) significantly inhibited tumor growth in human multiple myeloma xenograft mouse model[4].
References:
[1] Yoshimura C, Muraoka H, Ochiiwa H, et al. TAS4464, a highly potent and selective inhibitor of NEDD8-activating enzyme, suppresses neddylation and shows antitumor activity in diverse cancer models[J]. Molecular Cancer Therapeutics, 2019, 18(7): 1205-1216.
[2] Ochiiwa H, Ailiken G, Yokoyama M, et al. TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia[J]. Oncogene, 2021, 40(7): 1217-1230.
[3] Muraoka H, Yoshimura C, Tsuji S, et al. TAS4464, a novel highly potent NEDD8 activating enzyme inhibitor, demonstrates antitumor activity in multiple myeloma through the inactivation of NF-κB pathways[J]. Cancer Research, 2015, 75(15_Supplement): 1730-1730.
[4] Muraoka H, Yoshimura C, Kawabata R, et al. Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways[J]. Cancer Science, 2019, 110(12): 3802-3810.
TAS4464是一种高效且选择性的NEDD8激活酶（NAE）抑制剂，IC50为0.955nM。TAS4464具有优异的抗肿瘤活性，且靶点抑制作用持久[1]。TAS4464常用于急性髓系白血病[2]和多发性骨髓瘤[3]的研究。
TAS4464（0.1μM；0，8和24小时）可显著诱导急性髓系白血病HL-60细胞凋亡[2]。TAS4464（0.3-1000nM，72小时）可抑制多发性骨髓瘤细胞系的生长，并诱导其发生凋亡或有丝分裂性死亡[4]。
TAS4464（50或100mg/kg，每周两次；3周；静脉注射）显著抑制了人类多发性骨髓瘤异种移植小鼠模型中的肿瘤生长[4]。
| Cell experiment [1]: | |
Cell lines | Acute myeloid leukemia cell line HL-60 |
Preparation Method | HL-60 cells were treated with 0.1μM TAS4464 for 0, 8, and 24h. The harvested cells were stained with 5μl of Annexin V and 5μl of propidium iodide at room temperature in the dark. The cells were analyzed immediately by flow cytometry. |
Reaction Conditions | 0.1μM; 0, 8, and 24h |
Applications | TAS4464 significantly induced apoptosis in HL-60 cell line compared to the control. |
| Animal experiment [2]: | |
Animal models | Human multiple myeloma xenograft mouse model |
Preparation Method | Multiple myeloma cells were subcutaneously implanted into male Severe Combined Immunodeficiency (SCID) mice and allowed to grow to over 100mm3. Six animals were assigned to each group for each experiment, and TAS4464 formulated in 5% (w/v) glucose was administered intravenously twice a week at 50 or 100mg/kg. The individual therapies were performed for 3 weeks. Combinations of therapies followed the same administration schedules as the individual therapies for 3 weeks. Tumor volume was calculated with the following formula: [length × (width)2]/2. The vehicle for TAS4464 (5% [w/v] glucose) was used as the control for all treatments. |
Dosage form | 50 or 100mg/kg, twice a week; 3 weeks; i.v. |
Applications | TAS4464 significantly inhibited tumor growth in multiple myeloma mouse model. |
References: | |
| Cas No. | 1848959-10-3 | SDF | |
| Canonical SMILES | NC1=NC=NC2=C1C(C#CC3=C(F)C=CC=C3OCC)=CN2[C@@H]4O[C@H](CNS(=O)(N)=O)[C@@H](O)[C@H]4O | ||
| 分子式 | C21H23FN6O6S | 分子量 | 506.51 |
| 溶解度 | DMSO: 125 mg/mL (246.79 mM) | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9743 mL | 9.8715 mL | 19.7429 mL |
| 5 mM | 394.9 μL | 1.9743 mL | 3.9486 mL |
| 10 mM | 197.4 μL | 987.1 μL | 1.9743 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