NT157是一种具有选择性的胰岛素受体底物-1/-2（IRS-1/2）抑制剂。
Cas No.:1384426-12-3
Sample solution is provided at 25 µL, 10mM.
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NT157 is a selective inhibitor of insulin receptor substrate-1/-2 (IRS-1/2)[1]. IRS-1/2 are important cytoplasmic adaptor proteins that mediate insulin and insulin-like growth factor 1 (IGF-1) signaling, playing critical roles in glucose metabolism, cell growth, and development[2]. NT157 exerts its effects by inducing apoptosis and disrupting key signaling pathways and is commonly used in drug research and development for various diseases, including melanoma, prostate cancer, and colorectal cancer[3,4].
In vitro, pretreatment of osteosarcoma MG-63 and U-2OS cells with NT157 (3μM) for 24h significantly inhibited cell migration ability, accompanied by downregulation of IRS-2 protein[5]. Treatment of H1299 and H460 cells with NT157 (3.2, 6.4, 12.5μM) for 7 days resulted in a dose-dependent and significant inhibition of colony formation ability; at the concentration of 12.5μM, the colony formation rates of H1299 and H460 cells decreased to 1.4% and 0.8% of the control group, respectively[6].
In vivo, NT157 (100mg/kg; twice daily) was administered via intraperitoneal injection for 4 weeks in a nude mouse model of lung metastasis of hepatocellular carcinoma established by tail vein injection of SMMC-7721 cells, significantly reducing the incidence of lung metastasis compared to the control group[7]. NT157 (70mg/kg; thrice weekly) was administered via intravenous injection for 4 weeks in mice subcutaneously inoculated with A375SM cells, 48h after the final dose, pY(705)Stat3 levels in tumor tissues were significantly reduced[4].
References:
[1] DE QUEIROZ G N, LIMA K, DE MIRANDA L B L, et al. NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma[J]. Hematology, Transfusion and Cell Therapy, 2024, 46: S112-S121.
[2] RABIEE A, KRÜGER M, ARDENKJÆR-LARSEN J, et al. Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action[J]. Cellular Signalling, 2018, 47: 1-15.
[3] IBUKI N, GHAFFARI M, REUVENI H, et al. The tyrphostin NT157 suppresses insulin receptor substrates and augments therapeutic response of prostate cancer[J]. Molecular Cancer Therapeutics, 2014, 13(12): 2827-2839.
[4] FLASHNER-ABRAMSON E, KLEIN S, MULLIN G, et al. Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling[J]. Oncogene, 2016, 35(20): 2675-2680.
[5] GAROFALO C, CAPRISTO M, MANCARELLA C, et al. Preclinical effectiveness of selective inhibitor of IRS-1/2 NT157 in osteosarcoma cell lines[J]. Frontiers in Endocrinology, 2015, 6: 74.
[6] DE MIRANDA L B L, LIMA K, COELHO-SILVA J L, et al. NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells[J]. Scientific Reports, 2022, 12(1): 17092.
[7] YU S Z, WANG Y, LV K J, et al. NT157 inhibits HCC migration via downregulating the STAT3/Jab1 signaling pathway[J]. Technology in Cancer Research & Treatment, 2021, 20: 15330338211027916.
NT157是一种具有选择性的胰岛素受体底物-1/-2（IRS-1/2）抑制剂[1]。IRS-1/2是重要的细胞质结合蛋白，介导胰岛素和胰岛素样生长因子1（IGF-1）信号传导，在葡萄糖代谢、细胞生长和发育中发挥关键作用[2]。NT157通过诱导细胞凋亡和破坏关键信号通路起作用，通常用于黑色素瘤、前列腺癌和结直肠癌等多种疾病药物的研究和开发[3,4]。
在体外，NT157（3μM）预处理肉骨瘤MG-63和U-2OS细胞24h，显著抑制了细胞的迁移能力，并伴随IRS-2蛋白的下调[5]。NT157（3.2, 6.4, 12.5μM）处理H1299和H460细胞7天，可剂量依赖性地显著抑制克隆形成能力，在12.5μM浓度下H1299和H460细胞的克隆形成率分别降至对照组的1.4%和0.8%[6]。
在体内，NT157（100mg/kg; twice daily）通过腹腔注射治疗经尾静脉注射SMMC-7721细胞构建的肝癌肺转移裸鼠模型4周，较对照可显著降低小鼠的肺转移发生率[7]。NT157（70mg/kg; thrice weekly）通过静脉注射治疗皮下接种A375SM细胞的小鼠4周，末次给药48h后肿瘤组织中pY(705)Stat3水平显著降低[4]。
| Cell experiment [1]: | |
Cell lines | H1299 and H460 cells |
Preparation Method | H1299 and H460 cells were seeded at a density of 1×103 cells per well in 6-well plates and incubated for 24h, then treated with NT157 (3.2, 6.4, and 12.5μM) for 7 days. Colonies were fixed and stained with 1% crystal violet solution, and the number of colonies was counted to assess clonogenic capacity. |
Reaction Conditions | 3.2, 6.4, and 12.5μM; 7 days |
Applications | Treatment with NT157 significantly inhibited colony formation in a dose-dependent manner, reducing the colony formation rates of H1299 and H460 cells to 1.4% and 0.8% of the control group, respectively, at a concentration of 12.5μM. |
| Animal experiment [2]: | |
Animal models | Mice carrying A375SM xenograft tumors |
Preparation Method | A375SM cells were injected subcutaneously into mice, and administration of NT157 (70mg/kg) by intravenous injection was initiated 10 days later, thrice weekly for 4 weeks. Samples for immunohistochemistry were taken 48h following the last treatment. |
Dosage form | 70mg/kg; thrice weekly; 4 weeks; i.v. |
Applications | Treatment with NT157 significantly reduced the level of pY(705)Stat3 in tumor tissue. |
References: | |
| Cas No. | 1384426-12-3 | SDF | |
| 化学名 | (E)-3-(3-bromo-4,5-dihydroxyphenyl)-N-(3,4,5-trihydroxybenzyl)prop-2-enethioamide | ||
| Canonical SMILES | OC1=C(O)C=C(/C=C/C(NCC2=CC(O)=C(O)C(O)=C2)=S)C=C1Br | ||
| 分子式 | C16H14BrNO5S | 分子量 | 412.26 |
| 溶解度 | ≥ 50mg/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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4257 mL | 12.1283 mL | 24.2565 mL |
| 5 mM | 485.1 μL | 2.4257 mL | 4.8513 mL |
| 10 mM | 242.6 μL | 1.2128 mL | 2.4257 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。
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