RN486

RN486 is a potent, selective and orally active Btk inhibitor with an IC₅₀ of 4.0 nM and a K_d of 0.31 nM. RN486 is less active for other kinases. RN486 can be used for rheumatoid arthritis and systemic lupus erythematosus research^[1][2][3]. IC50 & Target: IC50: 4.0 nM (Btk)^[1]
Kd: 0.31 nM (Btk)^[1] 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)^[1].
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^[2]. 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^[1].