Icotrokinra

Description: Icotrokinra is an orally bioavailable and highly selective antagonist of the interleukin-23 receptor (IL-23R), thereby interfering with IL-23-mediated signaling cascades. Icotrokinra inhibits IL-23-induced STAT3 phosphorylation in peripheral blood mononuclear cells with an IC50 value of 5.6 pM, and it suppresses IL-23-induced interferon-gamma production in natural killer cells with an IC50 value of 18.4 pM. Icotrokinra further demonstrates anti-inflammatory effects in a rat TNBS-induced colitis model, making it a compound of interest in the study of psoriasis, psoriatic arthritis, and inflammatory bowel disease. Target: IL Receptor. Smiles: N(C([C@H](CC1=CC2=C(C=C1)C=CC=C2)NC([C@H](CC3=CC=C(OCCN)C=C3)NC(=O)[C@H]4NC(=O)[C@H](CCCCNC(C)=O)NC(=O)[C@H](CC=5C=6C(NC5)=C(C)C=CC6)NC(=O)[C@]([C@@H](C)O)(NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(C)=O)C(C)(C)SSC4(C)C)[H])=O)=O)C7(C(N[C@H](C(N[C@H](C(N[C@@H](CC=8C=CC=NC8)C(N(CC(N)=O)C)=O)=O)CC(N)=O)=O)CCC(O)=O)=O)CCOCC7. References: Fourie AM, et al., JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans. Sci Rep. 2024 Jul 30,14(1):17515.