Metarrestin

SKU: orb1941084

Description

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.

Key Properties

• CAS Number: 1443414-10-5
• MW: 474.608
• Purity: >98% (HPLC)
• Formula: C₃₁H₃₀N₄O
• SMILES: 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
• Target: eIF
• Solubility: In Vitro: DMSO : 31.25 mg/mL (65.84 mM)

Bioactivity

• In Vivo:
  Animal model: NOD/IL2 gamma (null) PANC1 mice over primary tumor tissues. 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. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ML246 | ML 246

Quick Database Links

Gene Symbol

eIF