Tyrosine kinase 2 (TYK2) is an intracellular tyrosine kinase protein that plays a vital role in immune responses in both innate and adaptive immunity. TYK2 as a target has significant effects on both IL-12/23 pathway and type Ⅰ interferon pathway. Both pathways have been implicated in various immune-mediated diseases. Targeting inhibition of TYK2 and its associated cytokine pathways has been validated in treating autoimmune diseases including psoriasis, systemic lupus erythematosus, etc.
AC-201, an allosteric TYK2/JAK1 inhibitor binding to JH2 domain, effectively inhibits TYK2/JAK1 activity through allosteric mechanisms. In Phase I study, AC-201 was safe and well-tolerated with no serious adverse events in healthy subjects. Phase II clinical trial of AC-201 in patients with moderate to severe plaque psoriasis is currently undergoing.
Plaque Psoriasis[12]
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Psoriasis is an immune-mediated, chronic, recurrent, inflammatory skin disease. The typical clinical manifestations of skin lesions are scaly erythema or plaques, which can be localized or widely distributed. Psoriasis is associated with joint damage, systemic diseases, and significant impairment in quality of life.
Biologics have revolutionized the treatment of Psoriasis. However, its immunogenicity may decrease the efficacy over time. Additionally, there are disadvantages such as injection administration and high cost. Biologics also increase the risk of infections, malignancies, and cardiovascular events. There is still a need for novel oral medications that can control the disease and reduce long-term adverse events.
[12] 中华医学会皮肤性病学分会银屑病专业委员会. 中国银屑病诊疗指南（2023版） [J] . 中华皮肤科杂志, 2023, 56(7) : 573-625.
