Identification of an Induced Orthosteric Pocket in IL-23: A New Avenue for Non-biological Therapeutic Targeting.

ABSTRACT: Interleukin 23 (IL23) is a key driver of autoimmune inflammatory pathology and has been successfully targeted by therapeutic antibodies for the treatment of psoriasis and ulcerative colitis. Identifying small-molecule inhibitors of IL23 signaling is of potential interest for drug development. We report the identification of an induced-fit orthosteric binding pocket on the IL23p19 subunit that may be suitable for small-molecule inhibition. X-ray crystallography was used to determine the structure of the IL23 heterodimer when bound to inhibitory peptide 23-446 and to confirm peptide binding to the IL23p19 subunit at the location of its interface with the IL23 receptor (IL23R). We then applied structure-based design to modify peptide 23-446. This process involved identifying key residues resp

SUBMITTER: Lecomte FC 

PROVIDER: S-EPMC12281479 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature