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[摘要]：The non-receptor tyrosine-protein kinase SYK (spleen tyrosine kinase) has a diverse range of biological functions, including a critical role in the intracellular signaling cascade for the surface immunoglobulin receptor on B lymphocytes and the Fc receptor expressed on numerous immune effector cells. It is therefore seen as a potential therapeutic target in a variety of conditions, including autoimmune, allergic and malignant diseases. Fostamatinib disodium is the orally bioavailable prodrug of R-406, a relatively selective small-molecule inhibitor of SYK, that has accordingly shown activity in numerous cell types in vitro, and efficacy in a remarkable range of animal models in vivo, including rodent models of asthma, inflammatory arthritis, lupus, glomerulonephritis, diabetes and lymphoma. Success in these models has translated to phase II clinical trials in autoimmune thrombocytopenia, lymphoma and, most notably, rheumatoid arthritis, in which larger phase Ill trials are currently in progress. While the diverse biological functions of SYK coupled with the potential off-target effects of this kinase inhibitor are a source of possible toxicity, the available data thus far augur well for future clinical use of fostamatinib in a wide range of human diseases. |
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