2-((4-(3,4-Dichlorophenyl)-thiazol-2-ylhydrazono)-3-(2-nitrophenyl))propionic acid (4EGI-1)
• A cell-permeable hydrazone compound that reversibly binds eukaryotic translation initiation factor 4E (eIF4E; Kd = 25 µM) and disrupts eIF4E/eIF4G, but not eIF4E/4E-BP1, complex formation.
OTAVAchemicals Catalogue Number: 7070707011
CAS Registry Number: 315706-13-9
Purity: 95%+ (HPLC)
Ref.: Moerke et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell (2007), 128, 257-267
Abstract: Assembly of the eIF4E/eIF4G complex has a central role in the regulation of gene expression at the level of translation initiation. This complex is regulated by the 4E-BPs, which competes with eIF4G for binding to eIF4E and which have tumor-suppressor activity. To pharmacological mimic 4E-BP function the authors developed a high-throughput screening assay for identifying small-mol. inhibitors of the eIF4E/eIF4G interaction. The most potent compound identified 4EGI-1, binds eIF4E, disrupts eIF4E/eIF4G association, and inhibits cap-dependent translation but not initiation factor-independent translation. While 4EGI-1 displaces eIF4G from eIF4E, it effectively enhances 4E-BP1 association both in vitro and in cells. 4EGI-1 inhibits cellular expression of oncogenic proteins encoded by weak mRNAs, exhibits activity against multiple cancer cell lines, and appears to have a preferential effect on transformed vs. nontransformed cells. The identification of this compound. provides a new tool for studying translational control and establishes a possible new strategy for cancer therapy.