Abstract
TYK2 (tyrosine-protein kinase 2) is a non-receptor protein kinase belonging
to the JAK family and is closely associated with various diseases, such as psoriasis, inflammatory
bowel disease, systemic lupus erythematosus. TYK2 activates the downstream
proteins STAT1-5 by participating in the signal transduction of immune factors
such as IL-12, IL-23, and IL-10, resulting in immune expression. The activity of the inhibitor
TYK2 can effectively block the transduction of excessive immune signals and
treat diseases. TYK2 inhibitors are divided into two types of inhibitors according to the
different binding sites. One is a TYK2 inhibitor that binds to JH2 and inhibits its activity
through an allosteric mechanism. The representative inhibitor is BMS-986165, developed
by Bristol-Myers Squibb. The other class binds to the JH1 adenosine triphosphate
(ATP) site and prevents the catalytic activity of the kinase by blocking ATP and downstream
phosphorylation. This paper mainly introduces the protein structure, signaling
pathway, synthesis, structure-activity relationship and clinical research of TYK2 inhibitors.
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http://dx.doi.org/10.1371/journal.pone.0122271] [PMID:
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