SBI-756

**SBI-756** is a first-in-class, small molecule inhibitor that targets **eukaryotic translation initiation factor 4G1 (eIF4G1)**, thereby disrupting the eIF4F translation initiation complex. This action leads to the selective reduction of cap-dependent mRNA translation, specifically decreasing translation of mRNAs encoding ribosomal proteins and translation factors, resulting in reduced protein synthesis rates in sensitive cancer cells. SBI-756 acts independently of mTOR signaling and does not affect mTOR substrate phosphorylation, offering potential advantages over mTOR inhibitors. It sensitizes cells, including those of diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ B-ALL), to standard therapies such as venetoclax and dasatinib, and has demonstrated synergistic apoptotic activity in vitro and in vivo. In melanoma models, SBI-756 impairs the growth of tumors resistant to BRAF inhibitors (BRAFi), including those with NRAS and NF1 mutations, and suppresses the emergence of BRAFi-resistant tumor clones. SBI-756 may also reduce AKT and NF-κB signaling, though derivatives with minimized off-target effects on these pathways have been developed. Preclinical studies indicate SBI-756 is well-tolerated and non-toxic at efficacious doses, and its unique mechanism positions it as a promising combination agent for overcoming drug resistance in aggressive cancers[1][3][4][5][6][7].

Other names

110-696-91997370