product name 4EGI-1
Description: 4EGI-1 is a competitive eIF4E/eIF4G interaction inhibitor by binding to eIF4E with KD of 25 μM. 4EGI-1 has been shown to amplify TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis via down-regulation of FLIPS/L and induction of DR5. These characteristics of the compound seem to be independent of its ability to inhibit cap-dependent protein translation which is caused by disruption of the eIF4E/eIF4G association through binding to eIF4E. It has been shown that while 4EGI-1 displaces eIF4G from eIF4E, it consequentially enhances 4E-BP association both in vivo and in vitro.
References: Cell. 2007 Jan 26;128(2):257-67; Neoplasia. 2010 Apr;12(4):346-56; Clin Cancer Res. 2013 Jun 15;19(12):3212-23.
451.28
Formula
C18H12Cl2N4O4S
CAS No.
315706-13-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 90 mg/mL (199.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 4EGI-1 disrupts the eIF4F complex and inhibits Cap-dependent translation in vitro. 4EGI-1 has proapoptotic activity in Jurkat cells, and potently inhibits cell growth with IC50 of approximately 6 μM in A549 lung cancer cells. 4EGI-1 augments TRAIL-induced apoptosis through induction of DR5 and down-regulation of c-FLIP, independent of inhibition of cap-dependent protein translation in human lung cancer cells. In addition, 4EGI-1, restores sensitivity to ABT-737 apoptosis through cap-dependent and -independent mechanisms in chronic lymphocytic leukemia. Kinase Assay: As a mimic peptide of 4E-BP, 4EGI-1 competes with eIF4G and disrupts the association of eIF4E/eIF4G. The KD value for 4EGI-1 binding to eIF4E is 25μM. 4EGI-1 can not affect the binding of 4E-BP to eIF4E and instead causes increase of this binding level. In addition, 4EGI-1 is found to inhibit the Cap-dependent translation while enhances the initiation factor-independent translation. In Jurkat leukemia T cells, 4EGI-1 also causes eIF4G to be displaced from eIF4E. Cell Assay: Cell viability is measured by treatment of Jurkat cells with compound for 24 h and by determination of intracellular ATP using the CellTiterGlo assay. For measurement of apoptotic DNA fragmentation, cells are treated for 24 h with 60 μM EGI-1 or 6.65 μM camptothecin in the presence or absence of 100 mM zVAD-FMK, a broad-spectrum caspase inhibitor. After fixation and staining with PI, cellular DNA content is determined by FACS analysis in a FACS Calibur machine. Nuclear morphology after 24 h EG1-1 treatment is visualized by staining of cells with Hoechst dye and fluorescence microscopy. For the A549 lung cancer cells, cell growth in the presence of 4EGI-1 is determined using the SRB staining method. |
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| References | Cell. 2007 Jan 26;128(2):257-67; Neoplasia. 2010 Apr;12(4):346-56; Clin Cancer Res. 2013 Jun 15;19(12):3212-23. |
