PI3Kδ-IN-8 is a powerful and specific oral inhibitor of PI3Kδ, exhibiting an IC50 of 3.3 nM. It demonstrates preferential inhibition of PI3Kδ when compared to PI3Kα, PI3Kβ, and PI3Kγ, with IC50 values of 377.2 nM, 241.6 nM, and 17.9 nM, respectively. Furthermore, PI3Kδ-IN-8 possesses notable anti-tumor efficacy.

PI3Kβ:241.6 nM (IC50), PI3Kα:377.2 nM (IC50), PI3Kγ:17.9 nM (IC50), PI3Kδ:3.3 nM (IC50)

PI3Kδ-IN-8 (compound 34) (0.1 nM-10 μM; 96 h) shows excellent potency against representative DLBCL cell lines, of either GCB (SUDHL-6), or ABC subtype (OCI-Ly10 and TMD-8)[1]. PI3Kδ-IN-8 (1 h) inhibits the PI3K-induced AKT phosphorylation in anti-IgM stimulated Raji cells, with an IC 50 of 9.5 nM[1]. Cell Viability Assay[1]Cell Line: SUDHL-6, OCI-Ly10, and TMD-8 cell lines Concentration: 0.1, 1, 10, 100, 1000, 10000 nM Incubation Time: 96 hours Result: Inhibited the viability of SUDHL-6, OCI-Ly10, and TMD-8 cells, with IC 50 s of <0.1 nM, <1 nM, and <0.1 nM, respectively.

PI3Kδ-IN-8 (1-30 mg/kg; p.o. once daily for 24 d) significantly reduces the tumor volume and tumor weight in a dose-dependent manner in mice[1]. PI3Kδ-IN-8 (1 mg/kg; i.v.) displays a suitable half-life (1 h), C max (2.3 μM) and low clearance (5.6 mL/min/kg) in mice[1]. PI3Kδ-IN-8 (10 mg/kg; p.o.) displays moderate oral bioavailability (39%), C max (7.5 μM), and AUC last (22 μM?h) in mice[1]. Animal Model: Female NOD scid mice were injected OCI-Ly10 cells[1]Dosage: 1, 3, 10, 30 mg/kg Administration: P.o. once daily for 24 days Result: Reduced the tumor volume, with an ED 50 of 6.47 mg/kg. Tumor growth inhibition of 81.95% was seen with a highly significant reduction in both tumor volume and tumor weight. Animal Model: Male BALB/c mice[1]Dosage: 1 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) Administration: Intravenous administration and oral administration Result: I.v.: t 1/2 =1 h, C max =2.3 μM, CL=5.6 mL/min/kg. P.o.: F=39%, C max =7.5 μM, AUC last =22μM?h.