TNFR1-selective miniprotein inhibitor

The TNFR1-selective miniprotein inhibitor is an orally available, protease-resistant de novo designed miniprotein that selectively binds and inhibits tumor necrosis factor receptor 1 (TNFR1) without binding to or blocking tumor necrosis factor receptor 2 (TNFR2) [Sa1434]. Developed by researchers at Northwestern University using generative AI-based protein design tools (including RFdiffusion, ProteinMPNN, and AlphaFold2/3), the miniprotein was optimized for high folding stability and resistance to gastrointestinal proteases (such as trypsin and chymotrypsin) using a lead scaffold designated as dp_b_2125 [Sa1434]. It is being investigated as a first-in-class oral biologic therapy for the treatment of inflammatory bowel disease (IBD), aiming to provide localized anti-inflammatory efficacy in the gut while avoiding the systemic side effects and loss of efficacy associated with traditional anti-TNF antibodies, as well as preserving the beneficial tissue repair pathways mediated by TNFR2 [Sa1434].

Other names

TNFR1-selective miniprotein inhibitorsTNFR-1-selective miniprotein inhibitorsTNFR 1-selective miniprotein inhibitors