Nemiralisib

Nemiralisib (GSK2269557 free base) is a potent and highly selective PI3Kδ inhibitor with a pK_i of 9.9. IC50 & Target: pKi: 9.9 (PI3Kδ)^[1]
pIC50: 5.3 (PI3Kα), 5.8 (PI3Kβ), 5.2 (PI3Kγ)^[1] In Vitro: Nemiralisib (GSK2269557 free base) is highly selective for PI3Kδ, with >1000-fold selectivity over the closely related isoforms PI3Kα (pIC₅₀=5.3), PI3Kβ (pIC₅₀=5.8) and PI3Kγ (pIC₅₀=5.2). Nemiralisib inhibits IFNγ in the peripheral blood mononuclear (PBMC) assay with an pIC₅₀ of 9.7^[1]. In Vivo: To assess the suitability of the series for inhaled delivery clearance data in rat microsomes and subsequently in vivo pharmacokinetic data from Sprague Dawley male rats is obtained. Compounds (e.g., Nemiralisib) are administered by the oral or intravenous routes, at a dose level of 3 and 1mg/kg respectively (n=2 rats/route). Nemiralisib free base is active in a disease relevant brown norway rat acute OVA model of Type 2 helper T-cells (Th2)-driven lung inflammation^[1].