Rheumatoid arthritis (RA) is a chronic disease characterized by bone joint damage and
incapacitation. The mechanism underlying RA pathogenesis is autoimmunity in the connective
tissue. Cytokines play an important role in the human immune system for signal transduction and
in the development of inflammatory responses. Janus kinases (JAK) participate in the JAK/STAT
pathway, which mediates cytokine effects, in particular interleukin 6 and IFN
. The discovery of
small molecule inhibitors of the JAK protein family has led to a revolution in RA therapy. The novel
JAK inhibitor upadacitinib (RinvoqTM) has a higher selectivity for JAK1 compared to JAK2 and JAK3
in vivo. Currently, details on the molecular recognition of JAK1 by upadacitinib are not available. We
found that characteristics of hydrogen bond formation with the glycine loop and hinge in JAKs define
the selectivity. Our molecular modeling study could provide insight into the drug action mechanism
and pharmacophore model differences in JAK isoforms.
� Copyright©2013. Inventi Journals Pvt.Ltd. All Right Reserved.