Nemiralisib (hydrochloride)

Nemiralisib hydrochloride (GSK2269557) 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 hydrochloride 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 hydrochloride 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 hydrochloride) are administered by the oral or intravenous routes, at a dose level of 3 and 1mg/kg respectively (n=2 rats/route). Nemiralisib hydrochloride is active in a disease relevant brown norway rat acute OVA model of Type 2 helper T-cells (Th2)-driven lung inflammation^[1].