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 (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.

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Perinucleolar compartment

Metarrestin (ML246) disrupts perinucleolar compartments in PC3M-GFP-PTB cells with an IC50 of 0.39 μM.
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).
Metarrestin (0.6 μM; 24 hours) effectively blocks the invasion of PC3M and PANC1 cells.
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.
has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Metarrestin (drug-infused chow; 10 mg/kg; 70 ppm) extends survival in the NSG PANC1 pancreatic cancer metastasis mice model.
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.
Metarrestin (5 and 25 mg/kg; IP) has a half-life of 4.6 to 5.5 hours.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

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

In Vitro: DMSO : 31.25 mg/mL (65.84 mM; Need ultrasonic)配制储备液