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ML327
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
ML327图片
CAS NO:1883510-31-3
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 366.38
Formula C19H18N4O4
CAS No. 1883510-31-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 30mg/mL
Water: N/A
Ethanol: N/A
Chemical Name N-(3-(2-oxo-1,2-dihydropyridine-3-carboxamido)propyl)-5-phenylisoxazole-3-carboxamide
Synonyms ML 327; ML327; ML-327;
实验参考方法
In Vitro

In vitro activity: ML327 de-represses E-cadherin transcription, partially reverses EMT, and inhibits cancer cell invasiveness and tumor cell migration in vitro and in vivo. Induction of E-cadherin mRNA expression by ML327 treatment does not require de novo protein synthesis. RNA sequencing analysis revealed that ML327 treatment significantly alters expression of over 2,500 genes within three hours in the presence of the translational inhibitor, cycloheximide. Network analysis reveals Hepatocyte Nuclear Factor 4-alpha (HNF4α) as the most significant upstream transcriptional regulator of multiple genes whose expressions were altered by ML327 treatment. Further, small interfering RNA-mediated depletion of HNF4α markedly attenuates the E-cadherin expression response to ML327. In summary, ML327 represents a valuable tool to understand mechanisms of EMT and may provide the basis for a novel targeted therapeutic strategy for carcinomas.


Kinase Assay: Treatment with ML327 induces an elongated morphology in neuroblastoma cells. BE(2)-C cells treated with ML327 demonstrates G1 cell cycle arrest with a concordant decrease in S phase population, and a significant increase in the sub G0 population. ML327 induces the expression of CDH1 in all seven of the neuroblastoma cell lines with a 50 to 1,400-fold induction of CDH1 mRNA expression. ML327 blocks the expression of MYC family of oncogenic transcription factors in all tested neuroblastoma cell lines. Immunoblotting time course demonstrates early repression of N-MYC expression within 2 h of treatment with ML327 (10 μM). p53 levels are also suppressed by treatment with ML327. ML327-pretreated cells demonstrates reduced proliferative potential in both tetrazolium-based (p<0.0001) and adherent 2D colony formation (41 vs. 400; p<0.0001). ML327 reduces SW620inv cell invasion through Matrigel by ~60% and reduces H520 cell invasion by ~30% in these in vitro assays. ML327 partially restores E-cadherin expression at the plasma membrane in NMuMG cells induced to undergo Epithelial-to-Mesenchymal Transition (EMT) by TGF-β1 treatment.


Cell Assay: 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.

In VivoML327 treatment significantly reduces tumor volume by three-fold over the two-week treatment period (p=0.02). Tumor explant weights are approximately three-fold smaller in the ML327-treated mice (p=0.01). Mice treated with ML327 lost 12% more body weight than vehicle treated mice. ML327 treatment results in a two-fold decrease in MYCN expression, confirming that ML327 inhibits xenograft MYCN expression (p=0.0035).
Animal modelAthymic nude mice
Formulation & Dosage50 mg/kg of ML327 or control vehicle (70% polyethylene glycol) via intraperitoneal injection twice daily for 14d.
References Oncotarget. 2017 Jul 20;8(53):91040-91051.