Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. Allergen-induced activation of the high-affinity receptor for IgE (FcεRI) in mast cells and basophils plays a pivotal role in the initiation of allergic and inflammatory reactions. As a result of receptor engagement, mast cells and basophils release a variety of inflammatory mediators, such as histamine, arachidonic acid metabolites, and cytokines. Moreover, Syk kinase can be activated in FcεRI-mediated signaling in mast cells.
The association of Syk with the ITAM of the γ subunit induces the phosphorylation and activation of Syk and stimulates subsequent signaling events, including activation of phospholipase C-γ1 (PLC-γ1) and protein kinase C (PKC). Thus it is possible that selective inhibitors of Syk or specific blockers of the association of Syk with ITAMs may prevent signaling by FcεRI. Now, we will introduce ER-27319, a Syk inhibitor.
ER-27319 is a Syk Inhibitor for inflammation diseases research.
ER-27319 (24 h) inhibits antigen-induced generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor α in RBL-2H3 cells, rat peritoneal and human cultured mast cells, and with an IC50 value of 10 μM. In addition, ER-27319 (10-30 μM, 10 min) selectivity inhibits the tyrosine phosphorylation of Syk induced by the phosphorylated immunoreceptor tyrosine-based activation motif of the FcεRI γ in RBL-2H3 cells. Besides, ER-27319 (100 μM, 10 min) inhibits the tyrosine phosphorylation of two proteins (38, 70 kD) and decreases the tyrosine phosphorylation of the other two proteins (62, 80 kD) in anti-IgG stimulation Canine cutaneous mastocytoma-derived cells.
All in all, ER-27319 is a promising Syk inhibitor for the study of inflammation and allergic diseases.
Reference:
[1] Moriya K, et al. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12539-44.
[2] Dinarello CA. Cell. 2010 Mar 19;140(6):935-50.