Size | Price | Stock | Qty |
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5mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
PIK-75 HCl, the hydrochloride salt of PIK-75, is a novel, potent, selective and imidazopyridine-based p110α inhibitor with potential anticancer activity and with IC50 of 5.8 nM, which is 200-fold more potent than p110β. Additionally, in cell-free assays, it strongly 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. The growth of HeLa cell xenografts in mouse models was inhibited by PIK-75 (at 50 mg/kg), according to in vivo studies. The p110 isoform of PI3K was the target of PIK-75 in acute myeloid leukemia (AML) cells, which resulted in the breakage of the link between Bcl-xL and Bak.
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 shows the impressive potency and isoform selectivity at p110α while the corresponding IC50 values are 1300 nM, 76 nM and 510 nM for other PI3K isoforms, p110β, -γ, and -δ, respectively. Furthermore, when binding to purified p110α, Additionally, PIK-75 is a competitive inhibitor of the substrate PI with a Ki of 2.3 nM and a noncompetitive inhibitor of ATP when binding to purified p110. [1] DNA-PK is effectively inhibited by PIK-75 as well. PIK-75 (1 μM) reduces cell survival by significantly decreasing mitochondrial activity in unstimulated nonasthmatic airway smooth muscle (ASM) cells, asthmatic ASM cells, and lung fibroblasts. While in TGFβ stimulated ASM cells, PIK75 has no effects on non-asthmatic cells and only reduces mitochondrial activity in asthmatic cells. [2] According to a recent study, PIK-75 (10 nM) significantly reduces TNF-α-induced ADP-ribosyl cyclase activity and TNF-α-induced CD38 mRNA expression in human airway smooth muscle cells.[3]
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ln Vivo |
In the ErbB3WT tumor model, PIK-75 lowers pAkt levels by 40% and lessens the in vitro chemotactic response to HRGβ1. Additionally, PIK-75 significantly lowers in vivo invasion and tumor cell motility in ErbB3WT primary tumors. [4] PIK-75 significantly impairs the insulin tolerance test (ITT), glucose tolerance test (GTT), and increases glucose production during the pyruvate tolerance test (PTT) in CD1 male mice.[5]
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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. The PI3K enzyme's activity is assessed in 50 μL of 20 mM HEPES, pH 7.5, 5 mM MgCl2, 180 μM phosphatidyl inositol, and 2.5 μCi of [γ-32P]ATP. The reaction is sparked by the addition of 100 μM ATP. The enzyme reaction is stopped by adding 50 μL of 1 M HCl after it has been incubated at room temperature for 30 minutes. Then, phospholipids are extracted using 250 μL of 2 M KCl and 100 ml of a 1:1 chloroform/methanol mixture to extract the phospholipids for liquid scintillation counting. Using Prism version 5.00 for Windows, the concentration versus inhibition of enzyme activity curve is created by diluting inhibitors in 20% (v/v) dimethyl sulfoxide. The IC50 is then calculated using this analysis. An assay that detects ATP consumption is used for kinetic analysis. PI and ATP are used at various concentrations to measure the activity of the PI3K enzyme in 50 L of 20 mM HEPES, pH 7.5, and 5 mM MgCl2. After a 60-minute incubation at room temperature, the reaction is stopped by adding 50 μL of Kinase-Glo, followed by an additional 15 minutes of incubation. The Fluostar plate reader is then used to read the luminescence. Prism is used to analyze the outcomes.
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Cell Assay |
Mitochondrial activity is measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay after stimulation with TGF with or without inhibitors for 48 hours. Before serial dilution (1:2) in duplicates, harvested washed cells are resuspended in DMEM-lO% FCS and aliquoted (500 μL) into 24-well cluster plates. Immediately after dilution, 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 to each well. The cells are then incubated for 3.5 hours at 37 °C. 500 μL of 10% sodium dodecyl sulfate (SDS) in 0.01 M HCl are added to each well to dissolve the resulting blue formazan product over the course of 16 hours at 37°C. In a 96-well microplate, a sample (150 μL) from each duplicate well is transferred, and the optical density is calculated using automated spectrophotometry in comparison to a reagent blank (no cells).A reference wavelength of 690 nm and a test wavelength of 570 nm are used to measure absorbance. Results from three to six wells from each treatment are averaged for each primary cell culture, and data are expressed as absorbance 570 to 690 nm.
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Animal Protocol |
MTLn3 cells are injected into the right fourth mammary fat pad from the head of female severe-combined immunodeficient/NCr mice.
≤1 μM Administered via i.p. |
References |
Molecular Formula |
C16H14BRN5O4S.HCL
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Molecular Weight |
488.74
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Elemental Analysis |
C, 39.32; H, 3.09; Br, 16.35; Cl, 7.25; N, 14.33; O, 13.09; S, 6.56
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CAS # |
372196-77-5
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Related CAS # |
PIK-75;372196-67-3
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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.Cl
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InChi Key |
VOUDEIAYNKZQKM-MYHMWQFYSA-N
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InChi Code |
InChI=1S/C16H14BrN5O4S.ClH/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;1H/b19-9+;
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Chemical Name |
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide;hydrochloride
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Synonyms |
PIK-75 hydrochloride; PIK-75 HCl; PIK75 HCl; PIK 75 HCl
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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) |
Solubility in Formulation 1: ≥ 1.1 mg/mL (2.25 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 11.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 1.1 mg/mL (2.25 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 11.0 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: ≥ 1.1 mg/mL (2.25 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: PIK-75 HCl; PIK75 HCl; PIK 75 HCl. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0461 mL | 10.2304 mL | 20.4608 mL | |
5 mM | 0.4092 mL | 2.0461 mL | 4.0922 mL | |
10 mM | 0.2046 mL | 1.0230 mL | 2.0461 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. td> |
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. td> |
PIK-75 potentiates gemcitabine-induced cytotoxicity in pancreatic cancer cells.Int J Oncol.2014 Mar;44(3):959-69. td> |
PIK-75 inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death.Int J Oncol.2014 Mar;44(3):959-69. td> |
PIK-75 enhances gemcitabine-induced apoptotic cell death and reduces MRP5 expression.Int J Oncol.2014 Mar;44(3):959-69. td> |