NSC 74859
(Synonyms: S3I-201;NSC74859;NSC-74859;S3I 201,) 目录号 : GC14653
NSC 74859是一种选择性STAT3抑制剂，IC50为86μM。
Cas No.:501919-59-1
Sample solution is provided at 25 µL, 10mM.
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NSC 74859 is a selective STAT3 inhibitor with an IC50 of 86μM[1]. STAT3(Signal Transducer and activator of Transcription 3), a pivotal transcription factor governing cell proliferation, survival and immune responses, is aberrantly activated in numerous cancers and inflammatory diseases[2]. NSC 74859 is mainly applied in tumor-targeted therapy, tumor immunology research[3][4].
In vitro, NSC 74859 (100μM; 48h) significantly inhibited STAT3 Tyr705 phosphorylation in HepG2, SK-HEP1 and Huh-7 human hepatoma cells, and synergically enhanced the antiproliferative activity of cetuximab[5].
In vivo, NSC 74859 (10mg/kg; p.o.; every other day for 14 days) attenuated cardiac allograft rejection and prolonged survival in mice by reducing infiltration of CD4⁺, CD8⁺ T cells and CD14⁺ monocytes/macrophages and by down-regulating IL-2, IL-15 and IL-6 expression within the graft[6]. NSC 74859(2.5mg/kg; i.p.; 16 weeks) significantly reduced renal collagen deposition, down-regulated fibrotic molecules (TGF-β1, ACE, AT1, VEGF), attenuated albuminuria, and reversed tubulointerstitial fibrosis and functional impairment in streptozocin-induced diabetic mice[7].
References:
[1] Siddiquee K, Zhang S, Guida WC, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A. 2007;104(18):7391-7396.
[2] Zou S, Tong Q, Liu B, Huang W, Tian Y, Fu X. Targeting STAT3 in Cancer Immunotherapy. Mol Cancer. 2020;19(1):145.
[3] Lin L, Amin R, Gallicano GI, et al. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling. Oncogene. 2009;28(7):961-972.
[4] Brady MT, Miller A, Sait SN, et al. Down-regulation of signal transducer and activator of transcription 3 improves human acute myeloid leukemia-derived dendritic cell function. Leuk Res. 2013;37(7):822-828.
[5] Chen W, Shen X, Xia X, et al. NSC 74859-mediated inhibition of STAT3 enhances the anti-proliferative activity of cetuximab in hepatocellular carcinoma. Liver Int. 2012;32(1):70-77.
[6] Lai Y, Kuang F, Shan Z, Liu H. A New Concept of the Old Inhibitor NSC 74859 in Alleviating Cardiac Allograft Rejection and Extending Allograft Survival in Mice. Ann Transplant. 2017;22:656-662.
[7] Zheng C, Huang L, Luo W, et al. Inhibition of STAT3 in tubular epithelial cells prevents kidney fibrosis and nephropathy in STZ-induced diabetic mice. Cell Death Dis. 2019;10(11):848.
NSC 74859是一种选择性STAT3抑制剂，IC50为86μM[1]。STAT3（信号转导与转录激活因子 3）是调控细胞增殖、存活及免疫反应的关键转录因子，其异常激活与多种癌症和炎症性疾病密切相关[2]。NSC 74859主要应用于肿瘤靶向治疗及肿瘤免疫学研究[3][4]。
体外实验中，NSC 74859（100μM；48h）显著抑制HepG2、SK-HEP1和Huh-7 三种人肝癌细胞的STAT3 Tyr705磷酸化，并与西妥昔单抗协同增强抗增殖活性[5]。
体内实验中，NSC 74859（10mg/kg；口服；隔日一次，共14天）通过减少心脏同种异体移植物内CD4⁺、CD8⁺ T细胞及CD14⁺单核/巨噬细胞的浸润，并下调IL-2、IL-15和IL-6的表达，显著减轻小鼠心脏排斥反应并延长移植物存活时间[6]。NSC 74859（2.5mg/kg；腹腔注射；16周）显著降低链脲佐菌素诱导的糖尿病小鼠肾脏胶原沉积，下调纤维化分子（TGF-β1、ACE、AT1、VEGF）表达，减轻蛋白尿，并逆转糖尿病引起的肾小管间质纤维化及功能损伤[7]。
| Cell experiment [1]: | |
Cell lines | HepG2, Huh-7 and SK-HEP1 cells |
Preparation Method | Human hepatoma cell lines (HepG2, SK-Hep1 and Huh-7) were propagated in RPMI-1640 medium, supplemented with 10% fetal bovine serum, 100 units/ml penicillin and 100mg/ml streptomycin. Cells were plated in six-well plates (2×105 cells/well) and treated with 100μM NSC 74859 for 48h. The cells were washed with ice-cold PBS and harvested in 100μl of cell lysis buffer containing protease inhibitors. Protein concentration of lysates was determined using the bicinchoninic acid (BCA) method. Cell lysates (40μg/lane) were separated using 10% SDS-PAGE, and transferred electrophoretically onto a polyvinylidene difluoride membrane. Membranes were blocked with tris-buffered saline TBS/0.1% Tween 20 (TBS/T) containing 5% bovine serum albumin and then incubated overnight at 4°C with anti-EGFR, phospho-STAT3 (Tyr705) or anti-STAT3 antibodies (1:1000). The membranes were washed thrice with TBS/T and incubated for 1h at room temperature with the appropriate secondary antibodies conjugated to goat anti-mouse horseradish peroxidase (1:2000). The membranes were washed and immunoreactive bands were developed using ECL and visualized using autoradiography on X-ray film. Protein loading was normalized by immunoblotting with a GAPDH antibody (1:5000). |
Reaction Conditions | 100μM; 48h |
Applications | NSC 74859 significantly inhibited STAT3 Tyr705 phosphorylation in HepG2, SK-HEP1 and Huh-7 human hepatoma cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6NHsd male and female mice |
Preparation Method | Six-week-old C57BL/6NHsd male and female mice, weighing 18–22 grams, housed and bred under Specific Pathogen Free (SPF) conditions. Homotopic heart transplantation was performed using microsurgery. Cold ischemia times were controlled to be less than 25min. Graft survival time was defined as the last day of transabdominally palpable cardiac contractions. Recipients remained untreated or were treated by oral gavage every other day for 14 days (6 treatments) with 10mg/kg NSC 74859. Control group mice were subjected to heart transplantation and treated with DMSO alone. The results, expressed as mean survival time ± standard deviation, were assessed for statistical significance by the Gehan survival test. myocardium samples were collected for real-time qPCR and Immunohistochemistry analyses. |
Dosage form | 10mg/kg; p.o.; every other day for 14 days |
Applications | NSC 74859 attenuated cardiac allograft rejection and prolonged survival in mice. |
References: | |
| Cas No. | 501919-59-1 | SDF | |
| 别名 | S3I-201;NSC74859;NSC-74859;S3I 201, | ||
| 化学名 | 2-hydroxy-4-[[2-(4-methylphenyl)sulfonyloxyacetyl]amino]benzoic acid | ||
| Canonical SMILES | CC1=CC=C(C=C1)S(=O)(=O)OCC(=O)NC2=CC(=C(C=C2)C(=O)O)O | ||
| 分子式 | C16H15NO7S | 分子量 | 365.36 |
| 溶解度 | ≥ 18.25mg/mL in DMSO | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 2.737 mL | 13.6851 mL | 27.3703 mL |
| 5 mM | 0.5474 mL | 2.737 mL | 5.4741 mL |
| 10 mM | 0.2737 mL | 1.3685 mL | 2.737 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。
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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