Introduction of Ustekinumab

Ustekinumab (L04AC05) is a humanized IgG1κ monoclonal antibody. It was designed to target interleukins IL-12 and IL-23, which are the member of interleukin 12 (IL-12) family cytokines. Ustekinumab acts as a human immunosuppressive drug used to treat psoriasis. Ustekinumab was approved by the U.S. Food and Drug Administration (FDA), Health Canada, and European Medicines Agency for the treatment of plaque psoriasis and psoriatic arthritis in 2009. Besides, the medication was approved by FDA for the treatment of moderate-severe Crohn's disease in September 2016.

Mechanism of Action of Ustekinumab

Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of an IL12B (IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit. Il-23 exerts its biological fnction through its functional receptor, which is composed of IL-12R β1 and IL-23R. IL-23 has been demonstrated to be related with IL-23- dependent differentiation and activation of Th-17 cells, IL-17 and IL-22 cytokine production and secretion. This results in synovium and skin inflammation as well as bone remodeling. IL-12 is a heterodimeric cytokine composed of two subunits, IL-12A (p35) and IL-12B (p40). Binding of IL-12 to its receptor, IL-12R, induces the transduction of cellular signal pathway known as JAK-STAT. Both IL-23 and IL-12 are considered as the key cytokines in inflammatory diseases. Ustekinumab is designed to bind specifically to the p40 subunit of IL-12 and IL-23, blocking their interaction with their receptors. This inhibits the downstream Th-17 signaling pathways and interferes with the triggering of inflammatory response, disrupting the proinflammatory pathways in several chronic diseases.

Fig.1 Mechanism of action of Ustekinumab

What We Provide

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