Lin Pan, Juan Xu, Hongming Xie, Yingjun Zhang, Huanfeng Jiang, Yongqi Yao, Wanqing Wu
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引用次数: 0
Abstract
Janus kinase (JAK), a class of non-receptor tyrosine kinases, are essential in modulating the cytokine signaling cascade of cytokines associated with immune responses. Despite their potential in the treatment of autoimmune diseases, JAK inhibitors are associated with safety concerns, regarding cytokine suppression and significant side effects. Tyrosine kinase 2 (TYK2), a prominent member of the JAK family, is central to the signaling of interleukins (ILs) and interferons (IFNs), such as IL-12, IL-23 and IFNs. Targeted TYK2 inhibitors that specifically target the Janus Homology 1 (JH1) and pseudokinase (JH2) domains show enhanced specificity. JH1 acts as an ATP-competitive inhibitor, while JH2 acts as an allosteric regulator, contributing to reduced systemic side effects and improved therapeutic outcomes in clinical settings. This review summarizes the recent advances on the synthetic strategies of TYK2 inhibitors and their applications in the treatment of autoimmune diseases.
期刊介绍：
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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