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You are here:Home-Inhibitors & Agonists-Nuclear Receptor/Transcription Factor-Eukaryotic Initiation Factor (eIF)

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Eukaryotic initiation factors (eIFs) are proteins involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of the functional ribosome around the start codon and also provide regulatory mechanisms in translation initiation.

Eukaryotic initiation factor 2B (eIF2B) is a guanine nucleotide-exchange factor which mediates the exchange of GDP (bound to initiation factor eIF2) for GTP, thus regenerating the active [eIF2.GTP] complex that is required for peptide-chain initiation. The activity of eIF2B is a key control point for eukaryotic protein synthesis and is altered in response to viral infection, hormones, nutrients, growth factors and certain stresses.

Eukaryotic translation initiation factor 4E (eIF4E) is best known for its function in the initiation of protein synthesis on capped mRNAs in the cytoplasm. Eukaryotic initiation factor (elF) 4A functions as a subunit of the initiation factor complex elF4F, which mediates the binding of mRNA to the ribosome.

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2BAct (eIF2B activator 2BAct) is a novel, highly selective, CNS-permeable small molecule eIF2B activator with EC50 of 33 nM in cell-based reporter assays; 2BAct normalized body weight gain and prevented motor deficits in male R191H mice, prevented myelin loss and reactive gliosis in the brain and spinal cord of R191H mice; also prevented ISR induction in the cerebellum and spinal cord of Eif2b5R132H/R132H mice, prevented all measures of pathology and normalizes the transcriptome and proteome of Vanishing White Matter (VWM) mice.




4EGI-1 is a competitive eIF4E/eIF4G interaction inhibitor with Kd of 25 uM (binding to eIF4E); disrupts eIF4E/eIF4G association and inhibits cap-dependent translation; inhibits cellular expression of oncogenic proteins encoded by weak mRNAs, exhibits activity against multiple cancer cell lines.


Pateamine A


Pateamine A (Pateamine) is a potent small molecule inhibitor of eukaryotic translation that stimulates eIF4AI/II and eIF4AIII activity, but not eIF4E, eIF2α, and elF4B; inhibits protein synthesis showing an IC50 of 5 nM in HeLa cells; prevents muscle wasting caused by IFNγ and TNFα or by C26-adenocarcinoma tumours in mice.




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.


eIF4A3 inhibitor 53a


eIF4A3 inhibitor 53a(eIF4A3-IN-53a) is a potent, selective and cell-active eukaryotic initiation factor 4A3 (eIF4A3) inhibitor with IC50 of 0.26 uM, SPR Kd of 43 nM; displays no activity against eIF4A1, eIF4A2, DHX29 and BRR2 ATPase (IC50>100 uM); binds to a non-ATP binding site of eIF4A3, exhibits cellular nonsense-mediated RNA decay (NMD) inhibitory activity and represents a novel molecular probe for further study of eIF4A3, the exon junction complex (EJC) and NMD.


eIF4A3 inhibitor 2


eIF4A3 inhibitor 2(eIF4A3-IN-2) is an allosteric, selective, non-competitive eIF4A3 inhibitor with IC50 of 0.11 uM, exhibits noncompetitive inhibition with ATP or RNA and high selectivity for eIF4A3 over other helicases; suppresses the helicase activity of eIF4A3 in an ATPase-dependent manner; targets the exon junction complex (EJC) and suppresses monsense-mediated mRNA decay.




Elatol (NSC 341593) is a specific inhibitor of ATP hydrolysis by eIF4A1 in vitro with broad activity against multiple tumor types; binds in a 2:1 ratio to eIF4A1 (Kd=1.98 uM) and disrupts helicase activity, Elatol is active against eIF4A1’s ATP hydrolysis at 16.4 uM; Elatol is less potent in vitro than the well-studied eIF4A1 inhibitor silvestrol but is tolerated in vivo at ~100X relative dosing, leading to significant activity against lymphoma xenografts.




Hippuristanol is a potent, steroid inhibitor of eukaryotic initiation factor 4A (eIF4A), results in cell cycle arrest at G1 phase, and induces caspases activation and apoptosis; also reduces the expression of cyclin D2, CDK2, CDK4, CDK6 and prosurvival XIAP and Mcl-1 proteins; significantly inhibits the growth and invasion of PEL cells in mice.

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