Structural Basis for p19 Targeting by Anti-IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis.

ABSTRACT: IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40; however, the structural composition of the IL-23-binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis

SUBMITTER: Daniele SG 

PROVIDER: S-EPMC10914523 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature