Abstract 1928 Peptide-based allosteric inhibitor targets TNFR1 conformationally active region and disables receptor–ligand signaling complex

Objective: Tumor necrosis factor (TNF) receptor 1 (TNFR1) is crucial for mediating TNF-induced signaling and regulating inflammatory responses. This study aimed to investigate the functional efficacy and mechanism of action of a novel anti-inflammatory peptide (FKCRRWQWRMKK, termed FKC) to inhibit TNFR1 signaling. Methods: A combination of biophysical, biochemical, and cellular assays, along with molecular dynamics simulations, was employed to characterize the interaction between FKC and TNFR1. Functional efficacy of FKC was evaluated in HEK293 cells and a mouse model of TNF-induced inflammation.