in vitro
In cell-based assays, Baricitinib phosphate proves to be a potent inhibitor of JAK signaling and function. In PBMCs, Baricitinib inhibits IL-6-stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50 values of 44 nM and 40 nM, respectively. In isolated naive T-cells, INCB028050 also inhibits pSTAT3 stimulated by IL-23 (IC50=20 nM). Importantly, this inhibition prevented the production of two pathogenic cytokines (IL-17 and IL-22) produced by Th17 cells-a subtype of helper T cells with demonstrable inflammatory and pathogenic properties-with an IC50 value of 50 nM. In stark contrast, the structurally similar but ineffective JAK1/2 inhibitors INCB027753 and INCB029843 has no significant effect in any of these assays systems when tested at concentrations up to 10 μM.
References
[1] fridman js, scherle pa, collins r, burn tc, li y, li j, covington mb, thomas b, collier p, favata mf, wen x, shi j, mcgee r, haley pj, shepard s, rodgers jd, yeleswaram s, hollis g, newton rc, metcalf b, friedman sm, vaddi k. selective inhibition of jak1 and jak2 is efficacious in rodent models of arthritis: preclinical characterization of incb028050. j immunol. 2010;184(9):5298-307.
