IC-87114

 Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	IC-87114 is a selective PI3Kδ inhibitor with IC50 of 0.5 μM, 58-fold more selective for PI3Kδ than PI3Kγ, and over 100-fold more selective than PI3Kα/β.
Targets	PI3Kδ	PI3Kβ	PI3Kγ
IC50	0.5 μM	75 μM	29 μM [1]
In vitro	IC-87114 selectively inhibits PI3Kδ and not sensitive to PI3Kα, β, and γ. In human neutrophils, IC87114 (5 µM) potently inhibits N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated phosphatidylinositol triphosphate (PIP3) biosynthesis and chemotaxis. IC87114 (5 µM) 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 µM) inhibits both constitutive and Flt-3-stimulated Akt phosphorylation and cell proliferation. [2] It is also found that IC87114 (5 µM–30 µM) inhibits SCF- or IL-3-stimulated BMMC responses, which are not observed in PI3Kδ mutant (p110δD910A) cells. [3] In anti-CD3-stimulated mice CD62L+ (naive) and CD62L− (effector/memory) CD4+ T cells, IC87114 inhibits proliferation and interferon-gamma (IFN-γ) production. The IC50 values of IC87114 are: (1) 1.2 µM and 40 nM, for CD62L+ and CD62L− cell proliferation, respectively; (2) 120 nM and 1 nM, for IFN-γ 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]
In vivo	In mice, IC87114 (15 mg/kg–60 mg/kg) inhibits the allergic response in the back skin and ear. [3] In mice induced with anti-CD3 or ConA, IC87114 (30 mg/kg) reduces hypersensitivity responses and decreases plasma levels of cytokines, such as IL-2, IL-4, IL-17, IFN-γ, and tumor necrosis factor-α (TNF-α). [4]
Features

Protocol(Only for Reference)

Kinase Assay: 

^[1]

PI3K kinase assay

Phosphatidylinositol-(4,5)-bisphosphate (PIP2) containing phospholipid liposomes are prepared. Briefly, bovine PIP2 and phosphatidylserine (1:2 molar ratio) are vacuum-dried and resuspended at 1 mM PIP2 in 20 mM HEPES-KOH, pH 7.4, 50 mM NaCl, and 5 mM EDTA. The lipid suspension is subjected to a brief sonication, followed by 5 freeze-thaw cycles and then 20 extrusion cycles to produce the liposomes. The assay is conducted in 60 μL reaction volumes in 20 mM HEPES, pH 7.4, buffer containing 1 nM PI3K, 1 µM PIP2, 200 µM ATP, 1 µCi [γ-32P]ATP, 5 mM MgCl2, plus 50 µg/mL horse IgG as carrier protein. The reaction is incubated for 10 min at room temperature, quenched in 140 of 1 M K2PO4, 30 mM EDTA, pH 8.0, captured onto a 96-well polyvinylidene difluoride filter plate, and washed five times with 1 M K2PO4. The filter is allowed to dry completely, and the bound radioactivity is quantitated. IC87114 dilutions are assayed in a final concentration of 1% (w/w) DMSO.

Cell Assay: 

^[2]

Cell lines	Human bone marrow mononuclear cells (BMMCs) and CD34+ cells
Concentrations	0–100 μM
Incubation Time	48 hours
Method	For AML cell proliferation assay, BMMCs are isolated and cultured in α-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 μCi [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 μM IC87114 and pulsed for 12 hours with [3H]-thymidine.

Animal Study: 

^[3]

Animal Models	Wild-type or PI3Kδ mutant (p110δD910A) mice (C57BL/6 or BALB/c)
Dosages	15 mg/kg–60 mg/kg
Administration	Oral gavage
Solubility	30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL

1

References

Chemical Information

Download IC-87114 SDF

Chemical Name	2-((6-amino-9H-purin-9-yl)methyl)-5-methyl-3-o-tolylquinazolin-4(3H)-one

Customer Reviews (3)

Click to enlarge	Rating
	Source	J Mass Spectrom, 2012, 47(12), 1612-1619 . IC-87114 purchased from Selleck
	Method	Within-assay/Between-assay
	Cell Lines	wistar rats
	Concentrations	5 mg/kg
	Incubation Time	1-24 h
	Results	Table 1 shows the results obtained for the within batch and between batch precision and accuracy for IC87114, RFM and RFN. The precision (% C.V) for all these analytes under investigation did not exceed 15%. Accuracy (% Nominal) for all analytes were in the range from 90.7% to 105.1% at any of the concentrations studied and met the requirements of validation.

Product Citations (7)

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  Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent. [Ni J, et al. Cancer Discov 2012;2(5):425-33]

  
  PubMed: 22588880


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  Vertical inhibition of the mTORC1/mTORC2/PI3K pathway shows synergistic effects against melanoma in vitro and in vivo. [Werzowa J, et al. J Inves Der 2010;131(2):495-503]

  
  PubMed: 21048785


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  PERK Utilizes Intrinsic Lipid Kinase Activity To Generate Phosphatidic Acid, Mediate Akt Activation, and Promote Adipocyte Differentiation. [Bobrovnikova-Marjon E, et al. Mol Cell Biol 2012;32(12):2268-78]

  
  PubMed: 22493067