货号：A940826同义名：
eIF4E/eIF4G Interaction Inhibitor II
4E1RCat blocks interaction between eIF4E:eIF4G and eIF4E:4E-BP1, prevents assembly of the eIF4F complex and inhibits cap-dependent translation with IC50 ~4 μM.
Eukaryotic translation initiation is tightly regulated at the step of ribosome recruitment. This process involves binding of eukaryotic initiation factor (eIF) 4F complex to mRNA cap structures. eIF4F is composed of: eIF4E, the cap-binding protein; eIF4A, a DEAD-box RNA helicase; and eIF4G, a scaffolding protein that bridges the interaction between eIF4E and eIF4A. 4E1RCat is an inhibitor of eIF4E:eIF4G interaction with an IC50 an of ∼4 μM. It also blocks eIF4E:4E-BP1 interaction. 4E1RCat at 50 μM reduced 80S ribosome complex formation and this inhibition of ribosome recruitment to mRNA by 4E1RCat was cap-specific. 4E1RCat inhibited cap-dependent translation from FF/HCV/Ren in a dose dependent manner. It also inhibited cap-dependent production of Ren Luc from Ren/CrPV/FF. Furthermore, in Jurkat cells, 4E1RCat at 50 μM decreased polysomes, increased the fraction of 80S ribosomal subunits, and decreased levels of Mcl-1 and c-Myc proteins, two eIF4E-dependent mRNAs. In vivo, 4E1RCat (15 mg/kg daily for 5 d) could reverse chemoresistance in a Myc-driven lymphoma model, consistent with the idea that deregulated translation plays a role in this phenomenon[3].
作用机制
eIF4E has five shallow pockets that form an elongated binding site and could support small molecule interactions. 4E1RCat shows potential for binding to four of these pockets[3].
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