Anti-Human IL-23A (p19) (Risankizumab) (I-2160-25mg)

IL-23 is a member of the IL-12 family of proinflammatory and immunoregulatory cytokines1 and plays a key role in the differentiation and proliferation of type 17 helper T cells (Th17)2. IL- 23 exists as a heterodimer composed of the IL-12p40 subunit and a novel p19 subunit that is shared with IL-393. IL-23 activities lead to the production of Th17-derived pro-inflammatory cytokines IL-17 and IL-221. Additionally, IL-23 possesses potent anti-tumor and anti-metastatic activity in mouse models of cancer, suggesting a potential role for IL-23 in therapeutic treatment of cancer4. IL-23 also contributes to chronic inflammation of immune-mediated diseases including psoriasis and psoriatic arthritis2. Risankizumab is a humanized IgG monoclonal antibody that inhibits the proinflammatory effects of IL-23 by binding to and neutralizing its p19 subunit5. Risankizumab was generated by immunizing NMRI × C57/Bl6 mice with a hybrid mouse p40/human p19 recombinant cytokine6. The hybrid cytokine was produced in HEK293F mammalian cells as individual p40 and p19 subunits with no linker, similar to native cytokines. Antibodies with high affinity binding to recombinant human IL-23 and the ability to inhibit human IL-23-induced IL-17 production in mouse splenocytes were selected. Epitope mapping identified residues 89-107 and 118-132 as the IL-23 binding sites. Risankizumab binding prevents IL-23 receptor activation and disrupts the IL-23/Th17 axis5. Additionally, risankizumab inhibits IL-23 phosphorylation of STAT3 in human B- lymphoblastoid cell lines derived from human diffuse large cell lymphoma and inhibits induction of IL-17 production from human IL-23 stimulation in mouse splenocytes. Risankizumab is also known as ABBV-066 and BI 655066. Risankizumab has been approved for treatment of plaque psoriasis, psoriatic arthritis, Crohn’s Disease, and ulcerative colitis.