AM-8508

AM-8508 is an orally bioactive PI3Kδ inhibitor with an IC₅₀ of 0.016 μM. AM-8508 selectively inhibits PI3Kδ, thereby blocking AKT phosphorylation mediated by the B cell receptor. AM-8508 suppresses the formation of antigen-specific IgG and IgM in rats immunized with keyhole limpet hemocyanin. AM-8508 can be used for the research of inflammatory diseases^[1]. In Vitro:AM-8508 (Compound 1) potently and selectively inhibits the PI3Kδ subtype with an IC₅₀ of 0.016 μM, exhibiting 3638-fold, 111-fold and 363-fold selectivity over PI3Kα (IC₅₀ = 58.2 μM), PI3Kβ (IC₅₀ = 1.78 μM) and PI3Kγ (IC₅₀ = 5.8 μM), respectively^[1].
AM-8508 potently inhibits anti-IgM/CD40L-induced proliferation of human B cells, with an IC₅₀ of 0.0064 μM^[1].
AM-8508 potently inhibits anti-IgM-induced AKT phosphorylation in mouse splenic B cells, with an IC₅₀ of 0.0046 μM^[1].
AM-8508 potently inhibits anti-IgD-induced AKT phosphorylation in human whole blood, with a total IC₅₀ of 0.0027 μM and a free IC₅₀ of 1.0 nM^[1]. In Vivo:AM-8508 (0.03-3 mg/kg; p.o.; single administration) potently inhibits B cell activation-induced AKT phosphorylation in IgM_m mice^[1].
AM-8508 (0.003-0.3 mg/kg, p.o., once daily for 10 consecutive days) dose-dependently suppresses the keyhole limpet hemocyanin (KLH)-induced humoral immune response in female Lewis rats^[1].