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Purity: ≥98%
IC-87114 is a novel, potent, selective and ATP-competitive PI3Kδ inhibitor (p110delta-selective) with potential anticancer activity. In a cell-free assay, it has an IC50 of 0.5 M for inhibiting PI3Kδ , which is 58-fold more selective for PI3Kδ over PI3Kγ and > 100-fold more selective than PI3Kα/β. According to reports, IC87114 decreased neutrophil chemotaxis and PIP3 synthesis induced by FMLP. In a mouse model of inflammation, IC87114 also prevented neutrophils from releasing elastase when TNF1α was present. A decrease in Akt-phosphorylation and PDK1 enzyme activity after treatment of this cell type with IC87114 suggested that PI3Kδ is involved in TNFα-induced signaling. IC87114 significantly reduced naive and effector PI(3)K signaling induced by T-cell receptors in human memory T cells.
| Targets |
PI3Kδ (IC50 = 0.5 μM); PI3Kγ (IC50 = 29 μM); PI3Kβ (IC50 = 75 μM)
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|---|---|
| ln Vitro |
IC-87114 selectively inhibits PI3Kδ and not sensitive to PI3Kα, β, and γ. IC87114 (5 M) potently prevents phosphatidylinositol triphosphate (PIP3) biosynthesis and chemotaxis in human neutrophils when N-formyl-methionyl-leucyl-phenylalanine (fMLP) is stimulated. Additionally, the polarized morphology and spread of neutrophils are inhibited by IC87114 (5 µM). [1] IC87114 (10 µM) inhibits both constitutive and Flt-3-stimulated Akt phosphorylation and cell proliferation in human acute myeloid leukemia (AML) blast cells, such as bone marrow mononuclear cells (BMMCs). [2] Additionally, IC87114 (5 µM-30 µM) is found to inhibit BMMC responses induced by SCF or IL-3, which are not seen in PI3K mutant (p110D910A) cells.[3] IC87114 inhibits proliferation and interferon-gamma (IFN-) production in CD62L+ (naive) and CD62L (effector/memory) CD4+ T cells from mice that have been stimulated with anti-CD3. The IC50 values for IC87114 are as follows: (1) 1.2 M and 40 nM, respectively, for CD62L+ and CD62L cell proliferation; (2) 120 nM and 1 nM, respectively, for CD62L+ and CD62L cell IFN-production. Human T cells show the same effects induced by IC87114. [4] According to a recent study, IC87114 increases the PtdIns(4,5)P2 transient increase in chromaffin cells, which potentiates exocytosis. [5]
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| ln Vivo |
IC87114 (15 mg/kg–60 mg/kg) reduces allergic reactions in the ears and back skin of mice. [3] IC87114 (30 mg/kg) reduces hypersensitivity reactions and plasma levels of cytokines like IL-2, IL-4, IL-17, IFN-γ, and tumor necrosis factor (TNF-α) in mice induced with anti-CD3 or ConA.[4]
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| Enzyme Assay |
In a nutshell, bovine PIP2 and phosphatidylserine are vacuum-dried and then resuspended at 1 mM PIP2 in 20 mM HEPES-KOH, pH 7.4, 50 mM NaCl, and 5 mM EDTA. To create the liposomes, the lipid suspension goes through a quick sonication, five freeze-thaw cycles, and twenty extrusion cycles. The assay is carried out in 60 μL reaction volumes with buffer containing 20 mM HEPES, pH 7.4, 1 µCi PI3K, 1 mM PIP2, 200 mM ATP, 1 ci [γ-32P]ATP, 5 mM MgCl2, and 50 µg/mL horse IgG as carrier protein. The reaction is incubated for 10 min at room temperature, quenched in 140 ml 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 bound radioactivity is measured after the filter has dried completely. Dilutions of IC87114 are evaluated at a final concentration of 1% (w/w) DMSO.
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| Cell Assay |
For the AML cell proliferation assay, BMMCs are isolated and cultured in the presence or absence of FLT-3 ligand (10 ng/mL) for 48 hours, as well as with or without IC87114, in a medium containing 5% fetal calf serum (FCS). The final 6 hours of the experiment involve the addition of [3H]-thymidine (1 μCi [37 kBq]) , and the radioactivity incorporated is measured by trichloracetic acid precipitation. The stem cell factor (SCF; 20 ng/mL), FLT-3 ligand (10 ng/mL), Tpo (20 nM), and CD34+ cells from cord blood are cultured for 48 hours with or without 10 μM IC87114 and pulsed for 12 hours with [3H]-thymidine.
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| Animal Protocol |
Mice: On day 0, BALB/c mice are given a single immunization by intraperitoneal injection of 10 µg of ovalbumin (OVA) dissolved in 0.2 ml of alu-Gel-S. Mice are given OVA (30 µg in 50 µL PBS) or PBS, once daily for four days, via intranasal (i.n.) challenge ten days later. Six treatment groups (A–F, 10–30 animals per group) were created to examine whether ERK1/2, PI3Kδ , and NF-κB are signaling effectors that act after EGFR transactivation.
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| References |
| Molecular Formula |
C22H19N7O
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|---|---|
| Molecular Weight |
397.43256
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| Exact Mass |
397.1651
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| Elemental Analysis |
C, 66.49; H, 4.82; N, 24.67; O, 4.03
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| CAS # |
371242-69-2
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| Related CAS # |
371242-69-2
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| Appearance |
Solid powder
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| SMILES |
O=C1N(C2=CC=CC=C2C)C(CN3C=NC4=C(N)N=CN=C34)=NC5=C1C(C)=CC=C5
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| InChi Key |
GNWHRHGTIBRNSM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19N7O/c1-13-6-3-4-9-16(13)29-17(27-15-8-5-7-14(2)18(15)22(29)30)10-28-12-26-19-20(23)24-11-25-21(19)28/h3-9,11-12H,10H2,1-2H3,(H2,23,24,25)
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| Chemical Name |
2-((6-amino-9H-purin-9-yl)methyl)-5-methyl-3-o-tolylquinazolin-4(3H)-one
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| Synonyms |
IC87114; IC-87114; IC 87114
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~0.66 mg/mL (~1.7 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: <1 mg/mL (slightly soluble or insoluble) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 4%DMSO+30%PEG 300+ddH2O: 0.7mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5162 mL | 12.5808 mL | 25.1617 mL | |
| 5 mM | 0.5032 mL | 2.5162 mL | 5.0323 mL | |
| 10 mM | 0.2516 mL | 1.2581 mL | 2.5162 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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Nature. 2004 Oct 21;431(7011):1007-11. |
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