RN-486

A potent and selective BTK inhibitor with IC50 of 4 nM in the enzymatic assay; shows high selectivity against a panel of 369 kinases; blocks Fcε receptor cross-linking-induced degranulation in mast cells (IC50=2.9 nM) and Fcγ receptor engagement-mediated TNFα production in monocytes (IC50=7.0 nM); robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models.Rheumatoid Arthritis Preclinical(In Vitro):RN486 blocks Fcε receptor cross-linking-induced degranulation in mast cells (IC50 = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC50 = 7 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC50 = 21 nM).In a co-culture system consisting of human primary synovial FLS and activated human platelets, convulxin stimulation resulted in elevated production of pro-inflammatory cytokines, IL-6 and IL-8, an effect which is dose-dependently blocked by RN486.(In Vivo):RN486 produces robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 (1-30 mg/kg) inhibits both joint and systemic inflammation, reducing both paw swelling and inflammatory markers in the blood.