Metarrestin

Metarrestin (ML246) is a specific inhibitor of perinuclear compartment (PNC), disrupts PNCs in PC3M-GFP-PTB cells with IC50 of 0.39 uM, specifically binds eEF1A2; reduces PNC prevalence in different human cancer cell lines at 1 uM (IC100 for PC3M cells) for 24 hours; disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, by interacting with the translation elongation factor eEF1A2inhibits cancer cell invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects. (In Vitro) :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. (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.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.

1443414-10-5

ML246 | ML 246

>98% (HPLC)

In Vitro: DMSO : 31.25 mg/mL (65.84 mM)

O[C@H]1CC[C@H] (N (C=NC2=C3C (C4=CC=CC=C4) =C (C5=CC=CC=C5) N2CC6=CC=CC=C6) C3=N) CC1

C31H30N4O

474.608

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.