| CAS |
No.1883510-31-3 |
| 英文名称 |
ML327 |
| 分子式 |
C19H18N4O4 |
| 分子量 |
366.37 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD31619239 |
| SMILES |
C1=CC=C(C=C1)C2=CC(=NO2)C(=O)NCCCNC(=O)C3=CC=CNC3=O |
| InChIKey |
NNNDNXLMQAPQQQ-UHFFFAOYSA-N |
| InChI |
InChI=1S/C19H18N4O4/c24-17-14(8-4-9-20-17)18(25)21-10-5-11-22-19(26)15-12-16(27-23-15)13-6-2-1-3-7-13/h1-4，6-9，12H，5，10-11H2，(H，20，24)(H，21，25)(H，22，26) |
| PubChem CID |
60167648 |
| 靶点 |
c-Myc |
| 通路 |
Apoptosis |
| 背景说明 |
ML327 是 MYC 的阻断剂，也可以去阻遏 E-钙粘蛋白转录和逆转上皮-间质转化 (EMT)。 |
| 生物活性 |
ML327 is a blocker of MYC which can also de-repress E-cadherin transcription and reverse Epithelial-to-Mesenchymal Transition (EMT).[1-2] |
| In Vitro |
用 ML327 处理可诱导神经母细胞瘤细胞的细长形态。用 ML327 处理的 BE (2)-C 细胞显示 G1 细胞周期停滞，S 期细胞群一致减少，而亚 G0 细胞群显著增加。ML327 在所有七种神经母细胞瘤细胞系中诱导 CDH1 的表达，CDH1 mRNA 表达诱导 50 到 1，400 倍。ML327 在所有测试的神经母细胞瘤细胞系中阻断致癌转录因子 MYC 家族的表达。免疫印迹时间进程表明在使用 ML327 (10 μM) 处理后 2 小时内 N-MYC 表达的早期抑制。p53 水平也被 ML327 处理抑制。ML327 预处理的细胞在基于四唑盐的 (p[1]中均表现出降低的增殖潜力。在这些体外测定中，ML327 通过 Matrigel 减少 SW620inv 细胞侵袭约 60%，并将 H520 细胞侵袭减少约 30%。在通过 TGF-β1 处理诱导上皮-间质转化 (EMT) 的 NMuMG 细胞中，ML327 部分恢复质膜上的 E-钙粘蛋白表达[2]。 |
| In Vivo |
ML327 处理在两周处理期间显著减少了三倍的肿瘤体积 (p=0.02)。ML327 处理的小鼠的肿瘤外植体重量大约小三倍 (p=0.01)。用 ML327 处理的小鼠比载体处理的小鼠多失去 12% 的体重。ML327 处理导致 MYCN 表达降低两倍，证实 ML327 抑制异种移植物 MYCN 表达 (p=0.0035)[1]。 |
| 细胞实验 |
Cells are seeded onto 96-well plates at equivalent density (3，000 to 10，000 depending upon cell line)， permitted to attach overnight， and treated with either ML327 (10 μM) or vehicle. Daily absorbance measurements (450 nm) using the cell counting kit are obtained. For estimation of IC50 values， cells are plated at equal density， permitted to attach， and baseline absorbance is obtained using cell counting kit. Cells are then treated with varying doses of ML327 (0.1 to 30 μM) and cell viability is measured 72 h after treatment[1]. |
| 动物实验 |
Male athymic nude mice (4 to 6 weeks old) are maintained as described. BE(2)-C cells xenografts are established as previously described. Briefly， 1×106 cells/100 μL of HBSS are injected subcutaneously into flanks using a 26-gauge needle (n=10 per group). Mice are monitored daily for xenograft formation and assessed by measuring the two greatest perpendicular tumor diameter with venier calipers. Xenograft volumes are estimated using the following formula [(length×width2)/2]. Once tumors reach 75 to 100 mm3， mice are randomized to receive either 50 mg/kg of ML327 or control vehicle (70% polyethylene glycol) via intraperitoneal injection twice daily for 14d. Weight and tumor volume are recorded daily. After completion of two weeks of treatment， mice are euthanized and tumors are excised， weighed， and RNA is isolated[1]. |
| 数据来源文献 |
[1]. Rellinger EJ， et al. Isoxazole compound ML327 blocks MYC expression and tumor formation in neuroblastoma. Oncotarget. 2017 Jul 20;8(53):91040-91051.
[2]. An H， et al. Small molecule/ML327 mediated transcriptional de-repression of E-cadherin and inhibition of epithelial-to-mesenchymal transition.Oncotarget. 2015 Sep 8;6(26):22934-48. |
| 规格 |
1mg 5mg 10mg 25mg |
| 单位 |
瓶 |
中文
英语
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