IC-87114

PI3K

397, 43

Wild-type or PI3Kdelta mutant (p110deltaD910A) mice (C57BL/6 or BALB/c)

0–100 uM

Dissolved in 75% PEG200

IC-87114 selectively inhibits PI3Kdelta and not sensitive to PI3Kalpha, beta, and gamma. In human neutrophils, IC87114 (5 uM) potently inhibits N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated phosphatidylinositol triphosphate (PIP3) biosynthesis and chemotaxis. IC87114 (5 uM) also inhibits polarized morphology and spreading of neutrophils. [1] In human acute myeloid leukemia (AML) blast cells, such as bone marrow mononuclear cells (BMMCs), IC87114 (10 uM) inhibits both constitutive and Flt-3-stimulated Akt phosphorylation and cell proliferation. [2] It is also found that IC87114 (5 uM–30 uM) inhibits SCF- or IL-3-stimulated BMMC responses, which are not observed in PI3Kdelta mutant (p110deltaD910A) cells. [3] In anti-CD3-stimulated mice CD62L+ (naive) and CD62L (effector/memory) CD4+ T cells, IC87114 inhibits proliferation and interferon-gamma (IFN-gamma) production. The IC50 values of IC87114 are: (1) 1.2 uM and 40 nM, for CD62L+ and CD62L cell proliferation, respectively, (2) 120 nM and 1 nM, or IFN-gamma production of CD62L+ and CD62L cells, respectively. Similar effects by IC87114 are also observed in human T cells. [4] A recent study reveals that in chromaffin cells, IC87114 enhances the transient increase of PtdIns(4, 5)P2, which results in a potentiation of exocytosis. [5]

48 hours

For AML cell proliferation assay, BMMCs are isolated and cultured in alpha-medium with 5% fetal calf serum (FCS) with or without FLT-3 ligand (10 ng/mL) for 48 hours and with or without IC87114. [3H]-thymidine (1 uCi [37 kBq]) is added for a final 6 hours and the amount of radioactivity incorporated is determined by trichloracetic acid precipitation. CD34+ cells from cord blood are cultured in stem cell factor (SCF, 20 ng/mL), FLT-3 ligand (10 ng/mL), and Tpo (20 nM) for 48 hours with or without 10 uM IC87114 and pulsed for 12 hours with [3H]-thymidine.

IC-87114 is a selective PI3Kδ inhibitor with IC50 of 0.5 μM in a cell-free assay, 58-fold more selective for PI3Kδ than PI3Kγ, and over 100-fold more selective than PI3Kα/β.