Therapeutics: Spleen tyrosine kinase (SYK)
In vitro and rat studies have identified a tetrahydropyranyldiamine-based SYK inhibitor that could help treat autoimmune diseases and cancer. Preclinical studies in models of rheumatoid arthritis (RA) and hematological malignancies have demonstrated a therapeutic benefit for SYK inhibition. A series of in vitro assays identified a tetrahydropyranyldiamine analog that selectively inhibited SYK at an IC50 value of 0.7 nM and showed no off-target ion channel interactions or mutagenic effects. In rats, the orally administered inhibitor had a half-life of 3.5 hours. Next steps could include testing the lead SYK inhibitor in animal models of RA.
Rigel Pharmaceuticals Inc. has the small molecule SYK inhibitor fostamatinib disodium in Phase III testing to treat idiopathic thrombocytopenic purpura (ITP). ...