Metarrestin

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Metarrestin (ML246) 是一种核周区室 (PNC) 的特异性抑制剂，可破坏 PC3M-GFP-PTB 细胞中的 PNC，IC50 为 0.39 uM。

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.

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Animal Model:NOD/IL2 gamma (null) PANC1 mice over primary tumor tissuesDosage:5 and 25 mg/kgAdministration: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.

ML246 | ML 246

Nuclear Receptor/Transcription Factor

eIF

eIF

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1443414-10-5

474.608

C31H30N4O

>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

Trans-4-(7-benzyl-4-imino-5,6-diphenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl) cyclohexanol

(-20℃)

With Ice Pack

≥ 2 years