FD223 是一种有效且选择性的磷酸肌醇3-激酶δ (PI3Kδ) 抑制剂。FD223 显示出高效价 (IC₅₀=1 nM) 和对其他异构体的良好选择性 (α、β 和 γ 的IC₅₀ 值分别为 51 nM、29 nM 和 37nM）。FD223通过抑制 p-AKT Ser473 有效抑制急性髓系白血病 (AML) 细胞系的增殖，从而导致细胞周期 G1 期阻滞。FD223 在 AML 等白血病的研究中具有潜力。

FD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. FD223 displays high potency (IC 50 =1 nM) and good selectivity over other isoforms (IC 50 s of 51 nM, 29 nM and 37 nM, respectively for α, β and γ). FD223 exhibits efficient inhibition of the proliferation of acute myeloid leukemia (AML) cell lines by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. FD223 has potential for the research of leukemia such as AML.

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PI3Kδ 1 nM (IC50) PI3Kα 51 nM (IC50

FD223 exhibits notable anti-proliferative activities in the p110δ-positive AML cell lines HL-60, MOLM-16, EOL-1 and KG-1, with the IC50 of 2.25 μM, 0.87 μM, 2.82 μM, and 5.82 μM, respectively. FD223 shows weak anti-proliferative activity against p110δ unexpressed MM.1R cell line, with the IC50 value of 23.13 μM.
FD223 (MOLM-16 cells; 0.1-5 μM; 16 hours) dose-dependently reduces phosphorylation of Akt (Ser473), which is consistent with the positive control Idelalisib, illustrating that the activity of PI3K/Akt pathway in MOLM-16 cell is blocked.
FD223 (MOLM-16 cells; 24 hours; 1-5 μM) arrests the cell cycle at the G1 phase similar to that of positive control Idelalisib.
FD223 (1-5 μM; 48 hours) dose-dependently induces cellular apoptosis. has not independently confirmed the accuracy of these method

FD223 (20 and 40 mg/kg; p.o, per day for 14 consecutive days) displays potent antitumor efficacy in MOLM-16 xenograft model with the tumor volume reduction of 49% at a dose of 40 mg/kg/day (po), and shows 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 with C =0.191 L?h?kg. In the po route, it shows a half-life (t 1/2 ) of 3.74 h and a Cmax of 1104 ng/mL, good oral plasma exposures (AUC 0-∞ >9000 h?ng/mL) and acceptable oral bioavailability (17.6%). has not independently confirmed the accuracy of these methods. They are for reference only.

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[1]. Yang C, et al. Bioisosteric replacements of the indole moiety for the development of a potent and selective PI3Kδ inhibitor: Design, synthesis and biological evaluation [published online ahead of print, 2021 Jun 21]. Eur J Med Chem. 2021;223:113661.

In Vitro: DMSO : 100 mg/mL (259.18 mM; Need ultrasonic)配制储备液