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Purity: ≥98%
PIK-75 is a p110α inhibitor with IC50 of 5.8 nM, which is 200-fold more potent than p110β. Additionally, in cell-free assays, it significantly inhibits DNA-PK, with an IC50 of 2 nM. In a variety of cell types, PIK-75, which was created as part of a PI 3-kinase drug discovery program, can attenuate insulin stimulation of Akt/PKB at a concentration of 100 nM. With an IC50 value in the range of 50 nM, PIK-75 has been shown to inhibit the growth of several different cell lines. PIK-75 inhibited the growth of HeLa cell xenografts in mice models when given at a dose of 50 mg/kg, according to in vivo studies. When PIK-75 attacked the p110 isoform of PI3K in acute myeloid leukemia cells, the connection between Bcl-xL and Bak was broken.
| Targets |
DNA-PK (IC50 = 2 nM); p110α (IC50 = 5.8 nM); p110γ (IC50 = 76 nM); p110δ (IC50 = 510 nM); p110β (IC50 = 1.3 μM); hsVPS34 (IC50 = 2.6 μM); PI3KC2β (IC50 = 1 μM); PI3KC2α (IC50 = 10 μM); mTORC1 (IC50 = 1 μM); mTORC2 (IC50 = 10 μM); ATM (IC50 = 2.3 μM); ATR (IC50 = 21 μM); PI4KIIIβ (IC50 = 50 μM)
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| ln Vitro |
PIK-75 also inhibits p110δ, PI3KC2β, mTORC1, ATM, hsVPS34, PI3KC2α, mTORC2, ATR and PI4KIIIβ with IC50s of 510 nM, ~1 μM, ~1 μM, 2.3 μM, 2.6 μM, ~10 μM, ~10 μM, 21 μM, ~50 μM, respectively[1].
With an IC50 of 1.2 M in L6 myotubes and 1.3 M in 3T3-L1 adipocytes, respectively, PIK-75 alone inhibits the phosphorylation of Thr 308[1]. With an IC50 value of 78 nM, PIK-75 (1–1000 nM; 5 min) inhibits the insulin-induced phosphorylation of PKB on Ser473 and Thr308 in CHO-IR cells in a dose-dependent manner. Through inducing apoptosis in pancreatic cancer cells, PIK-75 (0.1-1000 nM; 48 hours) prevents their growth and survival[3]. In addition, pancreatic cancer MIA PaCa-2 and AsPC-1 cells form fewer colonies when PIK-75 (0.1–1000 nM) is present[3]. |
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| ln Vivo |
PIK-75 (2 mg/kg) potentiates anticancer activity of Gemcitabine (20 mg/kg) in vivo. Gemcitabine (20 mg/kg) or PIK-75 (2 mg/kg) alone both significantly slow tumor growth. The combination of PIK-75 and Gemcitabine clearly has a positive effect because it significantly slows the growth of tumors in vivo while having no negative effects on the body weights of mice[3].
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| Enzyme Assay |
The PI3K inhibitor PIK-75 is dissolved at 10 mM in dimethyl sulfoxide and stored at −20°C until use. PI3K enzyme activity is determined in 50 μL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 containing 180 μM phosphatidyl inositol, with the reaction started by the addition of 100 μM ATP (containing 2.5 μCi of [γ-32P]ATP). After a 30-minute incubation at room temperature, the enzyme reaction is stopped by the addition of 50 μL of 1 M HCl. Phospholipids are then extracted with 100 μL of chloroform/methanol [1:1 (v/v)] and 250 μL of 2 M KCl followed by liquid scintillation counting. Inhibitors are diluted in 20% (v/v) dimethyl sulfoxide to generate a concentration versus inhibition of enzyme activity curve, which is then analyzed with the use of Prism version 5.00 for Windows to calculate the IC50. For kinetic analysis, a luminescent assay measuring ATP consumption is used. PI3K enzyme activity is determined in 50 μL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 with PI and ATP at various concentrations. After a 60-minute incubation at room temperature, the reaction is stopped by the addition of 50 μL of Kinase-Glo followed by a further 15-minute incubation. Luminescence is then read using a Fluostar plate reader. Results are analyzed using Prism.
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| Cell Assay |
Mitochondrial activity is assessed after stimulation with TGFβ with or without inhibitors for 48 hours using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Harvested washed cells are resuspended in DMEM-lO% FCS and aliquoted (500 μL) into 24-well cluster plates prior to serial dilution (1:2) in duplicates. To each well, 100 μL of an appropriate MTT concentration (dissolved in PBS and filtered through a 0.2 μm filter before use to remove any blue formazan product) is added immediately after diluting the cells, which are then incubated for 3.5 hours at 37 °C. The resulting blue formazan product is solubilized overnight (16 hours) at 37 °C by the addition of 500 μL of 10% sodium dodecyl sulfate (SDS) in 0.01 M HCl to each well. A sample (150 μL) from each duplicate well is transferred to a 96-well microplate, and the optical density determinedby automated spectrophotometry against a reagent blank (no cells). Absorbance is measured at a test wavelength of 570 nm and a reference wavelength of 690 nm. For each primary cell culture, results from three to six wells from each treatment are averaged, and data are expressed as absorbance 570 to 690 nm. Cells: A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852 cells.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C16H14BRN5O4S
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|---|---|
| Molecular Weight |
452.28
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| Exact Mass |
450.99499
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| Elemental Analysis |
C, 42.49; H, 3.12; Br, 17.67; N, 15.48; O, 14.15; S, 7.09
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| CAS # |
372196-67-3
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| Related CAS # |
PIK-75 hydrochloride;372196-77-5
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C=C(C=C1)[N+](=O)[O-])S(=O)(=O)N(C)/N=C/C2=CN=C3N2C=C(C=C3)Br
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| InChi Key |
QTHCAAFKVUWAFI-DJKKODMXSA-N
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| InChi Code |
InChI=1S/C16H14BrN5O4S/c1-11-3-5-13(22(23)24)7-15(11)27(25,26)20(2)19-9-14-8-18-16-6-4-12(17)10-21(14)16/h3-10H,1-2H3/b19-9+
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| Chemical Name |
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide
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| Synonyms |
PIK 75; PIK75; PIK-75
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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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2110 mL | 11.0551 mL | 22.1102 mL | |
| 5 mM | 0.4422 mL | 2.2110 mL | 4.4220 mL | |
| 10 mM | 0.2211 mL | 1.1055 mL | 2.2110 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.
RF2-knockdown reduces the proliferation of pancreatic cancer AsPC-1 cells.Int J Oncol.2014 Mar;44(3):959-69. |
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PIK-75 reduces NRF2 transcriptional activity in pancreatic cancer cells.
PIK-75 induces the proteasome-mediated degradation of NRF2.Int J Oncol.2014 Mar;44(3):959-69. |
 PIK-75 potentiates gemcitabine-induced cytotoxicity in pancreatic cancer cells.Int J Oncol.2014 Mar;44(3):959-69. |
PIK-75 inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death.Int J Oncol.2014 Mar;44(3):959-69. |
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PIK-75 enhances gemcitabine-induced apoptotic cell death and reduces MRP5 expression.Int J Oncol.2014 Mar;44(3):959-69. |
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