Metarrestin

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] 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].
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].