Metarrestin(Synonyms: ML246)

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Metarrestin (Synonyms: ML246) 纯度: 99.85%

Metarrestin (ML246) 是一种口服有效的，首创的，选择性的核周区室 (PNC) 抑制剂。Metarrestin 破坏核仁结构并抑制 RNA 聚合酶 (Pol) I 转录，部分是由于与翻译延伸因子 eEF1A2 的相互作用。Metarrestin 可以阻断小鼠癌症模型的转移发展，并延长存活期。

Metarrestin(Synonyms: ML246)

Metarrestin Chemical Structure

CAS No. : 1443414-10-5

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10 mM * 1 mL in DMSO ￥1775 In-stock
5 mg ￥1700 In-stock
10 mg ￥2900 In-stock
25 mg ￥5800 In-stock
50 mg ￥9900 In-stock
100 mg 询价

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生物活性

Metarrestin (ML246) is an orally active, first-in-class and specific perinucleolar compartment inhibitor. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2. Metarrestin blocks metastatic development and extends survival in mouse cancer models[1][2].

IC50 & Target

Perinucleolar compartment[1]
体外研究
(In Vitro)

Metarrestin (ML246) disrupts perinucleolar compartments in PC3M-GFP-PTB cells with an IC50 of 0.39 μM[2].
Metarrestin (1 μM; 24 hours) reduces perinucleolar compartment prevalence in different human cancer cell lines. Metarrestin impacts cell growth in cancer cell line PC3M but not in normal fibroblasts (GM02153)[2].
Metarrestin (0.6 μM; 24 hours) effectively blocks the invasion of PC3M and PANC1 cells[2].
Metarrestin (1 μM; 24 hours) does not significantly change the amounts of Pol I large subunit RPA194 and UBF in the three cell lines, PANC1, PC3M, and HeLa. Metarrestin shows a substantial reduction of 5’ETS RNA in cells[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.
体内研究
(In Vivo)

Metarrestin (ML246; 5-25 mg/kg; IP; once daily; continuing for six weeks) displays a decrease in metastatic burden in both liver (p <0.01) and lung with 25 mg/kg[2].
Metarrestin (drug-infused chow; 10 mg/kg; 70 ppm) extends survival in the NSG PANC1 pancreatic cancer metastasis mice model[2].
Metarrestin (5, 25 mg/kg; ip; for 4 additional week) reduces metastasis of prostate cancer (PC3M) and growth of metastatic breast cancer PDX mice models[2].
Metarrestin (5 and 25 mg/kg; IP) has a half-life of 4.6 to 5.5 hours[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.

Animal Model: NOD/IL2 gamma (null) PANC1 mice over primary tumor tissues[2]
Dosage: 5 and 25 mg/kg
Administration: IP; once daily; continuing for six weeks
Result: Displayed a decrease in metastatic burden in both liver (p <0.01) and lung with 25 mg/kg.
Demonstrated a significant reduction of perinucleolar compartment prevalence in metastatic and primary tumor tissues.
Animal Model: Female BALB/c mice[2]
Dosage: 5 and 25 mg/kg (Pharmacokinetic Analysis)
Administration: IP
Result: Indicated good exposure, distribution, and tolerability in vivo, with a half-life of 4.6 to 5.5 hours.

Clinical Trial

分子量

474.60

Formula

C31H30N4O
CAS 号

1443414-10-5
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 31.25 mg/mL (65.84 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1070 mL 10.5352 mL 21.0704 mL
5 mM 0.4214 mL 2.1070 mL 4.2141 mL
10 mM 0.2107 mL 1.0535 mL 2.1070 mL

*

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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 2.08 mg/mL (4.38 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.08 mg/mL (4.38 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Vilimas T, et al. Pharmacokinetic evaluation of the perinucleolar compartment disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer. Cancer Chemother Pharmacol. 2018 Dec;82(6):1067-1080.

    [2]. Frankowski KJ, et al. Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med. 2018 May 16;10(441).

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