PIK-75 HCl

Alias: PIK-75 hydrochloride; PIK-75 HCl; PIK75 HCl; PIK 75 HCl
Cat No.:V0116 Purity: ≥98%
PIK-75 HCl, the hydrochloride salt ofPIK-75, is a novel, potent, selective and imidazopyridine-basedp110α inhibitor with potential anticancer activity and with IC50 of 5.8 nM, which is 200-fold more potent than p110β.
PIK-75 HCl Chemical Structure CAS No.: 372196-77-5
Product category: PI3K
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
50mg
100mg
250mg
Other Sizes

Other Forms of PIK-75 HCl:

  • PIK-75
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
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)
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]
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]
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.
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.
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

[1]. Mol Pharmacol. 2011 Oct;80(4):657-64.

[2]. J Pharmacol Exp Ther. 2011 May;337(2):557-66.

[3]. Am J Respir Cell Mol Biol. 2012 Oct;47(4):427-35.

[4]. Oncogene. 2012 Feb 9;31(6):706-15.

[5]. Biochem J. 2012 Feb 15;442(1):161-9.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C16H14BRN5O4S.HCL
Molecular Weight
488.74
Elemental Analysis
C, 39.32; H, 3.09; Br, 16.35; Cl, 7.25; N, 14.33; O, 13.09; S, 6.56
CAS #
372196-77-5
Appearance
Solid powder
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
InChi Key
VOUDEIAYNKZQKM-MYHMWQFYSA-N
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+;
Chemical Name
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide;hydrochloride
Synonyms
PIK-75 hydrochloride; PIK-75 HCl; PIK75 HCl; PIK 75 HCl
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: ~4 mg/mL warming (~8.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
PIK-75 HCl; PIK75 HCl; PIK 75 HCl.
 (Please use freshly prepared in vivo formulations for optimal results.)
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.

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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Biological Data
  • PIK-75

    RF2-knockdown reduces the proliferation of pancreatic cancer AsPC-1 cells.2014 Mar;44(3):959-69.

  • PIK-75

    PIK-75 reduces NRF2 transcriptional activity in pancreatic cancer cells.


    PIK-75

    PIK-75 induces the proteasome-mediated degradation of NRF2.2014 Mar;44(3):959-69.

  • PIK-75

    PIK-75 potentiates gemcitabine-induced cytotoxicity in pancreatic cancer cells.2014 Mar;44(3):959-69.

  • PIK-75

    PIK-75 inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death.2014 Mar;44(3):959-69.

  • PIK-75

    PIK-75 enhances gemcitabine-induced apoptotic cell death and reduces MRP5 expression.2014 Mar;44(3):959-69.

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