ML327 is a blocker of MYC which can also de-repress E-cadherin transcription and reverse Epithelial-to-Mesenchymal Transition (EMT).

MYC^[1]

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)^[1]. 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^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

ML327 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)^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

366.37

C₁₉H₁₈N₄O₄

1883510-31-3

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 32 mg/mL (87.34 mM; Need ultrasonic and warming)

*

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, 6 months; -20°C, 1 month。-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。

• [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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.