Duvelisib (INK1197, IPI-145) is a selective inhibitor of phosphatidylinositol 3-kinase (PI3K) and p100δ, with effects on p110δ (IC50 value is 0.0025 μM), p110γ (IC50 value is 0.274 μM), p110β (IC50 value is 0.85 μM) and p110α (IC50 value is 1.602 μM).

PI3Kγ:243 pM(Ki), p110δ:2.5 nM, p110α:1602 nM, PI3Kδ:23 pM(Ki), p110β:85 nM, PI3Kβ:1564 pM(Ki), p110γ:27.4 nM

METHODS: Primary AML blasts (AML#2 and AML#5) were treated with Duvelisib (INK1197, IPI-145) (0.1, 0.5, 1 μM) and cultured for 4 hours. They were then incubated with BMSC conditioned medium for 5 minutes. Whole cell extracts were prepared and Western blot analysis was performed for pAKT (s473 and t308) and total AKT, as well as pMAPK and total MAPK.
RESULTS Duvelisib (INK1197, IPI-145) inhibited BMSC CM-induced pAKT (s473 and t308) activation at 0.1 μM; Duvelisib (INK1197, IPI-145) blocked blast migration through its inhibitory effect on AKT phosphorylation at the t308 site. [1]

METHODS: We used an Eμ-TCL1 adoptive transfer mouse model of CLL. After Duvelisib (INK1197, IPI-145) (100 mg/kg, once daily, oral, for 21 days),
RESULTS Duvelisib (INK1197, IPI-145) significantly reduced the CLL burden (CD19 CD5 B cells) in the peripheral blood of mice; at the same time, the total number of CD3 T cells in the mice was also lower, but the CD4/CD8 ratio was also reduced. [2]