NSC232003
目录号 : GC32721
NSC232003是一种靶向UHRF1的小分子抑制剂。
Cas No.:1905453-18-0
Sample solution is provided at 25 µL, 10mM.
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NSC232003 is a small molecule inhibitor targeting UHRF1 [1]. NSC232003 binds to the 5-methylcytosine recognition pocket of the SRA domain of UHRF1, thereby interfering with the interaction between UHRF1 and DNMT1, leading to a decrease in intracellular DNA methylation levels [2-3]. NSC232003 is primarily focused on tumor and epigenetic interventions [4].
In NRK-49F cells, NSC232003 (50μM; 1h) significantly reduced TGF-β1-induced KLF15 hypermethylation, while also decreasing the expression of α-SMA and fibronectin [5]. In fibroblasts, NSC232003 (5μM; 4h) exerts a significant anti-fibrotic effect by inhibiting the protein expression of fibrosis markers [6].
In KYSE450 cells xenograft mouse model, NSC232003 (5 mg/kg; ip; 3 weeks) significantly inhibited UHRF1 activity, and its combination with the DNMT inhibitor SGI-1027 more effectively suppressed NKX2-5/LHX1 expression and tumor growth by disrupting the UHRF1-DNMT positive feedback loop [7].
References:
[1]. Myrianthopoulos V, Cartron P F, Liutkevičiūtė Z, et al. Tandem virtual screening targeting the SRA domain of UHRF1 identifies a novel chemical tool modulating DNA methylation[J]. European journal of medicinal chemistry, 2016, 114: 390-396.
[2]. Patnaik D, Estève P O, Pradhan S. Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger–containing 1 (UHRF1) for anti-cancer drug development[J]. Oncotarget, 2018, 9(40): 26243.
[3]. Song Y, Liu H, Xian Q, et al. Mechanistic insights into UHRF1‑mediated DNA methylation by structure‑based functional clarification of UHRF1 domains[J]. Oncology Letters, 2023, 26(6): 542.
[4]. Kim A, Benavente C A. Oncogenic roles of UHRF1 in cancer[J]. Epigenomes, 2024, 8(3): 26.
[5]. Gu Y, Lv S, Huang X, et al. Inhibition of epigenetic regulator UHRF1 attenuates renal fibrosis and retains transcription factor Krüppel-like factor 15 expression[J]. Cell Death Discovery, 2025, 11(1): 270.
[6]. Cheng D, Wang Y, Li Z, et al. Liposomal UHRF1 siRNA shows lung fibrosis treatment potential through regulation of fibroblast activation[J]. JCI insight, 2022, 7(22): e162831.
[7]. Li X, Fan D, Li Y, et al. NKX2‐5/LHX1 and UHRF1 Establishing a Positive Feedback Regulatory Circuitry Drives Esophageal Squamous Cell Carcinoma through Epigenetic Dysregulation[J]. Advanced Science, 2025, 12(20): 2413508.
NSC232003是一种靶向UHRF1的小分子抑制剂 [1]。NSC232003与UHRF1 SRA结构域的5-甲基胞嘧啶识别口袋结合，从而干扰UHRF1与DNMT1的相互作用，导致细胞内DNA甲基化水平降低 [2-3]。NSC232003主要应用于肿瘤和表观遗传干预 [4]。
在NRK-49F细胞中，NSC232003（50μM；1h）显著降低了TGF-β1诱导的KLF15高甲基化，同时降低了α-SMA和纤连蛋白的表达 [5]。在成纤维细胞中，NSC232003（5μM；4h）通过抑制纤维化标志物的蛋白表达发挥显著的抗纤维化作用 [6]。
在KYSE450细胞异种移植小鼠模型中，NSC232003（5 mg/kg；ip；3周）显著抑制了UHRF1活性，并且它与DNMT抑制剂SGI-1027的组合通过破坏UHRF1-DNMT正反馈环路更有效地抑制了NKX2-5/LHX1表达和肿瘤生长 [7]。
| Cell experiment [1]: | |
Cell lines | NRK-49F cells |
Preparation Method | NRK-49F cells were starved overnight in DMEM containing 0% FBS prior to any stimulation. Pre-incubation of 50μM NSC232003 was carried out 1h before TGF-β1 treatment. The dosage levels and times of TGF-β1 were adopted as indicated. Cells were free from mycoplasma contamination. |
Reaction Conditions | 50μM; 1h |
Applications | NSC232003 significantly reduced TGF-β1-induced KLF15 hypermethylation, while also decreasing the expression of α-SMA and fibronectin. |
| Animal experiment [2]: | |
Animal models | KYSE450 cells xenograft mice tumor model |
Preparation Method | KYSE450 cells were implanted into BALB/c nude mice. One week later, the mice were randomly divided into four groups, receiving either the vector, NSC232003 (5mg/kg), SGI-1027 (5mg/kg), or a combination of NSC232003 and SGI-1027, respectively. The inhibitor was administered intraperitoneally for 3 weeks. Tumor size was measured every 3-4 days, and the tumor was resected 3 weeks after implantation. |
Dosage form | 5mg/kg; ip; once in 3 weeks |
Applications | NSC232003 significantly inhibited UHRF1 activity. When used in combination with the DNMT inhibitor SGI-1027, it can more effectively downregulate NKX2-5/LHX1 expression, block the UHRF1-DNMT positive feedback loop, and inhibit the growth of esophageal squamous cell carcinoma. |
References: | |
| Cas No. | 1905453-18-0 | SDF | |
| Canonical SMILES | O=C1NC(/C(C=N1)=C(NO)/C)=O | ||
| 分子式 | C6H7N3O3 | 分子量 | 169.14 |
| 溶解度 | Water : 17 mg/mL (100.51 mM);DMSO : < 1 mg/mL (insoluble or slightly soluble) | 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 | 5.9123 mL | 29.5613 mL | 59.1226 mL |
| 5 mM | 1.1825 mL | 5.9123 mL | 11.8245 mL |
| 10 mM | 591.2 μL | 2.9561 mL | 5.9123 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