Figure 3 Inhibitors of the IL-6/JAK/STAT3 signalling pathway

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Figure 3 Inhibitors of the IL-6/JAK/STAT3 signalling pathway Figure 3 | Inhibitors of the IL-6/JAK/STAT3 signalling pathway. Various targeted agents that inhibit different nodes of the IL-6 signalling pathway have been developed. Siltuximab, sirukumab, olokizumab, clazakizumab, and MEDI5117 are anti-IL-6 monoclonal antibodies. Tocilizumab and sarilumab are monoclonal antibodies that target IL-6R. These antibodies inhibit both the classic and trans-signalling pathways. By contrast, the gp130–Fc fusion protein olamkicept inhibits IL-6 trans-signalling but not the classic signalling pathway. Tofacitinib, ruxolitinib, pacritinib, and AZD1480 are small-molecule tyrosine kinase inhibitors that target JAKs, preventing phosphorylation of STAT3. C188-9, OPB-31121, OPB-51602, and other Src homology domain 2 (SH2) domain inhibitors interfere with STAT3 dimerization. The STAT3 antisense oligonucleotide AZD9150 binds to and causes the destruction of STAT3 mRNA, thus decreasing STAT3 expression. The cyclic STAT3 decoy contains a nucleotide sequence derived from the promoter of the STAT3 target gene FOS. This decoy competitively inhibits STAT3 binding to genomic response elements in the promoter regions of target genes. Johnson, D. E. et al. (2018) Targeting the IL‑6/JAK/STAT3 signalling axis in cancer Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2018.8