Identification and Characterization of Small-Molecule IRF3-Dependent Immune Activators for Pharmaceutical Development.

ABSTRACT: We sought to develop a small-molecule activator of interferon regulatory factor 3 (IRF3), an essential innate immune transcription factor, which could potentially be used therapeutically in multiple disease settings. Using a high-throughput screen, we identified small-molecule entities that activate a type I interferon response, with minimal off-target NFκB activation. We identified 399 compounds at a hit rate of 0.24% from singlicate primary screening. Secondary screening included the primary hits and additional compounds with similar chemical structures obtained from other library sources and resulted in 142 candidate compounds. The hit compounds were sorted and ranked to identify compound groups with activity in both human and mouse backgrounds to facilitate animal model engagement for

SUBMITTER: Foss MH 

PROVIDER: S-EPMC10064657 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature