Guselkumab (CNTO 1959) is a recombinant human IgG1 monoclonal antibody targeting the IL-23p19 subunit. Guselkumab binds to human cynomolgus monkey IL-23 with Kd values of 3.3 and 1.9 pmol/L, respectively. Guselkumab can inhibit the production of cytokines downstream of IL-23 signaling pathway, and can be used in the study of psoriatic arthritis.

IL-23:0.06 nM (IC50), IL-23 (monkey):1.9 pM, IL-23:0.06 pM(kd), IL-23 (human):3.3 pM, STAT3 phosphorylation:102.1100±2.0053 nM

Guselkumab effectively suppresses the production of Th17 cytokines, including IL17A, IL-17F, and IL-22, in mouse splenocytes stimulated with IL-23 concentrations of 0.5 or 1 ng/mL, demonstrating IC50 values between 0.016-0.080 nM. It also inhibits the IL-23 (10 or 100 ng/mL) driven production of IL-10 in human NKL cells. However, guselkumab does not impact the IL-12 (0.1 ng/mL) mediated production of interferon γ (IFNγ) in NK92MI cells. In combination with IBI112, guselkumab can prevent IL-23-induced STAT3 phosphorylation, showing an IC50 of 102.1100±2.0053 nM. Additionally, guselkumab blocks the induction of mIL-17 production by hIL-23 in a dose-dependent manner with an IC50 of 4.9743 ±1.2847 nM and inhibits IL-17F production in cynomolgus monkeys with an IC50 of 16.7950 nM.