Janus kinases (JAKs) are cytoplasmic tyrosine kinases. JAKs link cytokine signaling from membrane receptors to signal transducer and activator of transcription (STAT). Furthermore, the JAK-STAT signal pathway transfers the extra-membrane stimulus signal into the cell, thereby regulating downstream gene expression. Meanwhile, JAKs consist of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Of which, JAK1 and JAK2 are the main drivers of STAT3 phosphorylation and signal transduction. They act on STAT3, participate in many important biological processes such as cell inflammation and immune regulation. JAK1 and JAK2, involved in cytokine signaling, are important targets for the treatment of rheumatoid arthritis and COVID-19.
Baricitinib (LY3009104) is a potent, selective and orally active JAK1 and JAK2 inhibitor. Although, Baricitinib has demonstrable selection for JAK3, it is not inhibit JAK3 at a rather low concentration. Generally, this compound has the potential to study rheumatoid arthritis and COVID-19. In addition, Baricitinib inhibits JAK1 and JAK2 with the IC50 values of 5.9 nM and 5.7 nM, respectively. A research found that structurally similar compounds lacking JAK1/2 inhibitory activity were inactive in cellular cytokine assays. Certainly, the results suggest that Baricitinib inhibits JAK signaling and function initiated by cytokine. In mice, Baricitinib administration resulted in substantially reduced inflammation, CD8 infiltration, and MHC class I/II expression. Consequently, these show that a central role for JAK1/2 in these models systems and the selectivity of Baricitinib.
In conclusion, Baricitinib is a selective and orally active JAK1 and JAK2 inhibitor. Baricitinib inhibits inflammation and regulates the immune, which could provide an effective study for rheumatoid arthritis and COVID-19.