Cytokine Signalling Forum

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Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implication for SYK inhibitors in autoimmune disease therapy

Liao C, Hsu J, Kim Y et al. - Arthritis Research and Therapy 2013 15:R146

Spleen tyrosine kinase (SYK) has already been described as a potential therapeutic target for the treatment of autoimmune diseases. Previously the SYK inhibitor fostamatinib was in clinical development for the treatment of rheumatoid arthritis, but has since been suspended. However, investigation into SYK inhibition continues with RO2091, a novel ATP-competitive inhibitor of SYK with reasonable selectivity, potency and oral bioavailability which has been shown to suppress various innate and adaptive immune responses in vitro and in mCIA models. Following investigation in this study, including selectivity tests indicating no overlap into the JAK/STAT pathway, the authors conclude that RO2091 could serve as a promising medical lead for the design of SYK inhibitors, and could complement the current therapeutic agents in the treatment of inflammation-related and autoimmune disorders.