Spleen tyrosine kinase (Syk) has been identified as an important modulator of immune signaling in B cells and cells bearing Fcgamma-activating receptors. R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). We enrolled 189 patients with active RA despite methotrexate therapy in a 3-month, multicenter, ascending-dose, double-blind, placebo-controlled trial. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Twice-daily oral doses of 100 mg and 150 mg of R788 were significantly superior to placebo or twice-daily oral doses of 50 mg at week 12 (ACR20 achieved in 65% and 72% versus 38% and 32% of patients, respectively [P < 0.01]). ACR50 (achieved in 49% and 57% versus 19% and 17% of patients, respectively) and ACR70 (achieved in 33% and 40% versus 4% and 2% of patients, respectively) scores showed a similar pattern. Clinical effect was noted as early as 1 week after initiation of therapy. Reductions in serum interleukin-6 and matrix metalloproteinase 3 levels also occurred as early as week 1 in the groups receiving 100 mg and 150 mg R788. The major adverse effects were gastrointestinal side effects (predominantly diarrhea) and neutropenia (<1,500/mm3), both of which were dose related. These results indicate that an inhibitor of Syk kinase produces significant clinical benefits at 12 weeks in a population of patients with active RA receiving methotrexate therapy. Syk kinase may be an important new therapeutic target in RA and related autoimmune conditions.
Spleen tyrosine kinase ( Syk ) has been identified as an important modulator of immune signaling in B cells and cells bearing Fcgamma - activating receptors . R788 , a prodrug of active metabolite R406 , has been shown to be an inhibitor of Syk kinase , active in a variety of in vitro and in vivo models , suggesting potential activity in the treatment of rheumatoid arthritis ( RA ) . We enrolled 189 patients with active RA despite methotrexate therapy in a 3-month , multicenter , ascending - dose , double - blind , placebo - controlled trial . The primary end point was the American College of Rheumatology 20 % improvement criteria ( ACR20 ) response rate at week 12 . Twice - daily oral doses of 100 mg and 150 mg of R788 were significantly superior to placebo or twice - daily oral doses of 50 mg at week 12 ( ACR20 achieved in 65 % and 72 % versus 38 % and 32 % of patients , respectively [ P < 0.01 ] ) . ACR50 ( achieved in 49 % and 57 % versus 19 % and 17 % of patients , respectively ) and ACR70 ( achieved in 33 % and 40 % versus 4 % and 2 % of patients , respectively ) scores showed a similar pattern . Clinical effect was noted as early as 1 week after initiation of therapy . Reductions in serum interleukin-6 and matrix metalloproteinase 3 levels also occurred as early as week 1 in the groups receiving 100 mg and 150 mg R788 . The major adverse effects were gastrointestinal side effects ( predominantly diarrhea ) and neutropenia ( < 1,500/mm3 ) , both of which were dose related . These results indicate that an inhibitor of Syk kinase produces significant clinical benefits at 12 weeks in a population of patients with active RA receiving methotrexate therapy . Syk kinase may be an important new therapeutic target in RA and related autoimmune conditions .
Which enzyme is inhibited by a drug fostamatinib?
Which enzyme is inhibited by a drug fostamatinib ?
spleen tyrosine kinase
spleen tyrosine kinase