NU 9056
目录号 : GC11972
NU 9056（1，2-双（异噻唑-5-基）二硫烷）是一种有效且选择性的Tip60（KAT5） 组蛋白乙酰转移酶（HAT）抑制剂，IC50值为2μM，具有抗肿瘤活性。
Cas No.:1450644-28-6
Sample solution is provided at 25 µL, 10mM.
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NU 9056 (1,2-bis(isothiazol-5-yl) disulfide) is a potent and selective Tip60 (KAT5) histone acetyltransferase (HAT) inhibitor with an IC50 value of 2μM and anti-tumor activity[1, 2]. Tip60 regulates key biological processes such as gene transcription, DNA damage repair, and cell apoptosis by acetylation of histones (such as H4, H2A) and non-histone substrates[3]. NU 9056 is more than 16 times more selective for Tip60 than PCAF, p300, and GCN5[4].
In vitro, NU 9056 (2.5-40μM) treated human anaplastic thyroid carcinoma (ATC) cells (CAL-62 cells) for 48h effectively inhibited ATC cell proliferation in a concentration-dependent manner, reduced the expression levels of intracellular acetyl histone H2A and acetyl histone H4, and inhibited cell migration, invasion, and tube formation[5].
In vivo, NU 9056 (5mg/kg) treated with intraperitoneal injection in mice with lipopolysaccharide (LPS)-induced sepsis-associated encephalopathy (SAE) improved the survival rate of mice and alleviated cognitive impairment, anxiety, and depressive behaviors[6].
References:
[1] Coffey K, Blackburn T J, Cook S, et al. Characterisation of a Tip60 specific inhibitor, NU9056, in prostate cancer[J]. 2012.
[2] Xu L, Qin Y, Liu M, et al. The acetyltransferase KAT5 inhibitor NU 9056 promotes apoptosis and inhibits JAK2/STAT3 pathway in Extranodal NK/T cell lymphoma[J]. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents), 2022, 22(8): 1530-1540.
[3] Lashgari A, Tchara P E K, Lambert J P, et al. New insights into the DNA repair pathway choice with NuA4/TIP60[J]. DNA repair, 2022, 113: 103315.
[4] Dansu D K. Changes in the Epigenetic Landscape of Oligodendrocyte Progenitor Cells With Time[D]. City University of New York, 2023.
[5] Xu W, Xie L, Yang Y, et al. KAT5 Inhibitor NU9056 Suppresses Anaplastic Thyroid Carcinoma Progression through c‐Myc/miR‐202 Pathway[J]. International journal of endocrinology, 2022, 2022(1): 2014568.
[6] Chen L, Qing W, Yi Z, et al. NU9056, a KAT 5 inhibitor, treatment alleviates brain dysfunction by inhibiting NLRP3 inflammasome activation, affecting gut microbiota, and derived metabolites in LPS-treated mice[J]. Frontiers in Nutrition, 2021, 8: 701760.
NU 9056（1，2-双（异噻唑-5-基）二硫烷）是一种有效且选择性的Tip60（KAT5） 组蛋白乙酰转移酶（HAT）抑制剂，IC50值为2μM，具有抗肿瘤活性[1, 2]。Tip60通过乙酰化组蛋白（如H4、H2A）和非组蛋白底物，调控基因转录、DNA损伤修复、细胞凋亡等关键生物学过程[3]。NU 9056对Tip60的选择性比PCAF、p300和GCN5高16倍以上[4]。
在体外，NU 9056（2.5-40μM）处理人类间变性甲状腺癌（ATC）细胞（CAL-62 细胞）48h，以浓度依赖性方式有效抑制ATC细胞增殖，降低了细胞内乙酰组蛋白H2A和乙酰组蛋白H4的表达水平，抑制了细胞的迁移、侵袭和管腔形成[5]。
在体内，NU 9056（5mg/kg）通过腹腔注射治疗脂多糖（LPS）诱导的脓毒症相关脑病（SAE）小鼠，提高了小鼠的存活率，并减轻了认知障碍、焦虑和抑郁行为[6]。
| Cell experiment [1]: | |
Cell lines | Human Anaplastic thyroid carcinoma (ATC) cells ( CAL-62 cells) |
Preparation Method | Cells were plated into 96-well plates (4×103 cells/well), cultured overnight, and treated with NU 9056 (2.5-40μM) for 48h. Then, CCK-8 solution was added and incubated for 2h at 37°C. Next, the OD value was measured using a microplate reader at a wavelength of 450nm. |
Reaction Conditions | 2.5-40μM; 48h |
Applications | NU 9056 potently inhibited ATC cell proliferation in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 J mice |
Preparation Method | Ninety-five, 12-week-old C57BL/6J mice weighing 25-30g were randomly divided into a control group, a lipopolysaccharide (LPS) group, and an NU 9056 (LPS+NU 9056) group. LPS-treated mice received an intraperitoneal injection of LPS (10mg/kg). Control mice were injected with the same amount of normal saline. NU 9056 (5mg/kg) was intraperitoneally injected twice, 30min before and 24h after LPS injection. Sixteen hours after intraperitoneal injection of LPS, blood was collected transcardially. The supernatant was separated and collected. The experiment was performed immediately. Finally, the remaining samples were stored at -80°C. Another 43 mice were randomly divided into three groups with the same grouping and treatment methods as well as before. The animal survival rate and behavioral experiments were carried out. The mice were euthanized by intraperitoneal injection of sodium pentobarbital 150mg/kg. |
Dosage form | 5mg/kg; i.p. |
Applications | NU 9056 improved the survival rate of mice and alleviated LPS-induced cognitive impairment, anxiety, and depression in vivo. |
References: | |
| Cas No. | 1450644-28-6 | SDF | |
| 化学名 | 1,2-di(isothiazol-5-yl)disulfane | ||
| Canonical SMILES | C1(SSC2=CC=NS2)=CC=NS1 | ||
| 分子式 | C6H4N2S4 | 分子量 | 232.37 |
| 溶解度 | <10mg/ml in DMSO | 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 | 4.3035 mL | 21.5174 mL | 43.0348 mL |
| 5 mM | 0.8607 mL | 4.3035 mL | 8.607 mL |
| 10 mM | 0.4303 mL | 2.1517 mL | 4.3035 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
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- Purity: >98.00%
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