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.