Development of O'PROTACs-Based Novel EIF4G1 Degraders for Treatment of Non-Small Cell Lung Cancer
Abstract
Dysregulation of mRNA translation including the initiation process is a frequent feature of neoplasia including lung cancer, whereas most studies focus on the factors of eukaryotic initiation factor 4F (EIF4F) complex, EIF4E and EIF4A but not EIF4G. Although published data have demonstrated that EIF4G1 plays important roles in some cancer pathogenesis, progression and treatment, currently there are very limited EIF4G1 specific inhibitors available. In the current project, we have designed and synthesized a series of new EIF4G1 inhibitors by using oligonucleotide-based proteolysis-targeting chimera (OPROTAC) technology. Our screening results showed that most of these new compounds effectively reduced non-small cell lung cancer (NSCLC) cell growth, induced cell apoptosis and interfered with tumor cell cycle, through direct degradation of EIF4G1 protein. The identification of the signature of EIF4G1-controlled downstream proteins in NSCLC cells is still in process. Together, our data provide innovative translational and mechanistic insights into development of EIF4G1-targeted therapy in NSCLC patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2024
- Accession Number
- AD1229690
Entities
People
- Zhiqiang Qin
Organizations
- University of Arkansas for Medical Sciences