NCGC00378430是一种有效的SIX1/EYA2相互作用抑制剂。
Cas No.:920650-00-6
Sample solution is provided at 25 µL, 10mM.
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NCGC00378430 is a potent inhibitor of the SIX1/EYA2 protein-protein interaction[1]. NCGC00378430 disrupts the SIX1/EYA2 complex, reverses SIX1-induced TGF-β signaling activation, and counteracts the epithelial-mesenchymal transition (EMT) phenotype. NCGC00378430 is applicable in research areas such as breast cancer and pulmonary fibrosis[2-3].
In vitro, NCGC00378430 (10µM) was used to treat KIRC cells for 3 days. NCGC00378430 did not alter cell viability or proliferation, nor did NCGC00378430 impair the binding of SIX1 to the ITGB1 promoter. NCGC00378430 had no effect on SIX1-induced ITGB1 transcription, but did disrupt the SIX1-EYA2 interaction[1]. NCGC00378430 (10–20µM) was applied to MCF7-SIX1, T47D, and MDA-MB-231 breast cancer cell lines for 3 days. NCGC00378430 significantly disrupted the SIX1/EYA2 protein-protein interaction and reversed the TGF-β signaling activation and EMT phenotype induced by SIX1 overexpression[2].
In vivo, NCGC00378430 (25mg/kg) was administered via local injection (near the tumor cell injection site) every other day to NSG mice bearing MCF7-SIX1 tumors, from day 3 to day 21 post-injection. NCGC00378430 significantly inhibited breast cancer metastasis but did not affect the growth of the primary tumor[2]. NCGC00378430 (20mg/kg) was delivered intranasally every three days to either Six1 conditionally overexpressing mice (from day 3 to day 21) or wild-type C57BL/6 mice (from day 10 to day 21) in a bleomycin-induced pulmonary fibrosis model. NCGC00378430 alleviated fibrotic changes and enhanced lung function[3].
References:
[1] Huang S, Hu J, Hu M, et al. Cooperation between SIX1 and DHX9 transcriptionally regulates integrin-focal adhesion signaling mediated metastasis and sunitinib resistance in KIRC. Oncogene. 2024 Sep;43(39):2951-2969.
[2] Zhou H, Blevins MA, Hsu JY, et al. Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis. Cancer Res. 2020 Jun 15;80(12):2689-2702.
[3] Fan Y, Tian Z, Zheng H, et al. Six1 promotes alveolar epithelium senescence in pulmonary fibrosis through regulating Tp53. Int Immunopharmacol. 2025 Dec 3;166:115554.
NCGC00378430是一种有效的SIX1/EYA2相互作用抑制剂[1]。NCGC00378430可破坏SIX1/EYA2复合物、逆转SIX1诱导的TGF-β信号传导和上皮-间质转化（EMT）。NCGC00378430可用于乳腺癌和肺纤维化的相关研究[2-3]。
在体外，NCGC00378430（10μM）处理KIRC细胞3天。NCGC00378430不改变细胞活力与增殖，不阻碍SIX1与ITGB1启动子结合，对SIX1诱导的ITGB1转录无影响，但破坏SIX1-EYA2相互作用[1]。NCGC00378430（10–20μM）处理MCF7-SIX1、T47D及MDA-MB-231乳腺癌细胞3天。NCGC00378430显著破坏SIX1/EYA2蛋白相互作用，逆转SIX1过表达诱导的TGF-β信号通路激活与上皮-间质转化（EMT）表型[2]。
在体内，NCGC00378430（25mg/kg）隔天一次局部注射（于肿瘤细胞注射部位附近），用于处理携带MCF7-SIX1肿瘤的NSG小鼠，从注射后第3天持续至第21天。NCGC00378430显著抑制了乳腺癌的转移，但不影响原发肿瘤的生长[2]。NCGC00378430（20mg/kg）每三天一次滴鼻给药，用于处理博来霉素诱导的肺纤维化模型中的Six1条件性过表达小鼠（从第3天到第21天）或野生型C57BL/6小鼠（从第10天到第21天）。NCGC00378430减轻了纤维化改变并改善了肺功能[3]。
| Cell experiment [1]: | |
Cell lines | MCF7-SIX1 cells (human breast adenocarcinoma cell line with SIX1 overexpression), MCF7-Ctrl cells (control), T47D cells (human breast ductal carcinoma cell line), MDA-MB-231 cells (human breast adenocarcinoma cell line) |
Preparation Method | Cells were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS). MCF7-SIX1 and MCF7-Ctrl cells were treated with 10µM NCGC00378430 for 3 days. T47D and MDA-MB-231 cells were treated with 20µM NCGC00378430 for 3 days. |
Reaction Conditions | 10 or 20nM; 3 days. |
Applications | NCGC00378430 significantly disrupted the SIX1-EYA2 protein-protein interaction and reduced SIX1/EYA2 transcriptional activity. NCGC00378430 partially reversed transcriptional and metabolic profiles induced by SIX1 overexpression, including reversing gene expression signatures of epithelial-mesenchymal transition (EMT). In MCF7-SIX1 cells, NCGC00378430 suppressed TGF-β signaling (reduced phospho-SMAD3), restored membranous E-cadherin localization, and decreased fibronectin expression. |
| Animal experiment [2]: | |
Animal models | Six1 conditionally overexpressing mice (Six1-CTG) in alveolar epithelial cells and wild-type (WT) C57BL/6 mice. |
Preparation Method | Mice were treated with NCGC00378430 (20mg/kg) via transnasal delivery every three days. For the preventive regimen, treatment started on day 3 post-bleomycin (BLM) induction until day 21. For the therapeutic regimen in WT mice, treatment started on day 10 post-BLM induction until day 21. |
Dosage form | 20mg/kg; intranasal; every three days for 19 or 12 days. |
Applications | NCGC00378430 treatment attenuated fibrotic changes (reduced Ashcroft score and expression of Fibronectin and Collagen I), reduced inflammatory cell infiltration (decreased total protein in BALF), and improved declining lung function (increased compliance, reduced elastance) in BLM-induced pulmonary fibrosis models. NCGC00378430 showed both preventive and therapeutic effects. |
References: | |
| Cas No. | 920650-00-6 | SDF | |
| 分子式 | C22H23N3O5S | 分子量 | 441.5 |
| 溶解度 | DMSO : 100 mg/mL (226.50 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.265 mL | 11.325 mL | 22.6501 mL |
| 5 mM | 453 μL | 2.265 mL | 4.53 mL |
| 10 mM | 226.5 μL | 1.1325 mL | 2.265 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >99.50% Appearance: A solid
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