FD223 is a potent, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor with a marked affinity (IC50=1 nM), demonstrating notable selectivity against other isoforms (IC50s: α=51 nM, β=29 nM, γ=37 nM). This compound effectively suppresses the proliferation of acute myeloid leukemia (AML) cell lines by inhibiting p-AKT Ser473, thereby inducing G1 phase cell cycle arrest. FD223 holds promise for leukemia research, particularly in AML[1].

PI3Kα:51 nM (IC50), PI3Kβ:29 nM (IC50), PI3Kγ:37 nM (IC50), PI3Kδ:1 nM (IC50)

FD223 exhibits significant anti-proliferative activities in p110δ-positive AML cell lines HL-60, MOLM-16, EOL-1, and KG-1, with IC50 values of 2.25 μM, 0.87 μM, 2.82 μM, and 5.82 μM, respectively, while showing weak activity against the p110δ-negative MM.1R cell line (IC50: 23.13 μM)[1]. In MOLM-16 cells (0.1-5 μM; 16 hours), FD223 dose-dependently reduces Akt (Ser473) phosphorylation, akin to Idelalisib, indicating PI3K/Akt pathway inhibition[1]. FD223 also arrests the cell cycle at the G1 phase (1-5 μM; 24 hours) and induces cellular apoptosis in a dose-dependent manner (1-5 μM; 48 hours)[1].

FD223 (20 and 40 mg/kg; p.o, per day for 14 consecutive days) demonstrates potent antitumor efficacy in the MOLM-16 xenograft model, achieving a 49% tumor volume reduction at a dose of 40 mg/kg/day (po), and exhibits no significant toxicity in the preliminary safety assessment. FD223 (i.v.; dose of 2 mg/kg; p.o.; 10 mg/kg rats) shows a moderate plasma clearance rate after intravenous administration (C = 0.191 L·h^-1·kg^-1). When administered orally, it presents a half-life (t1/2) of 3.74 hours, a Cmax of 1104 ng/mL, good oral plasma exposures (AUC0-∞ > 9000 h·ng/mL), and acceptable oral bioavailability (17.6%).