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PIK-75 HCl

PIK-75 HCl

Item no.	S1205-5000
Manufacturer	Selleckchem
CASRN	372196-77-5
Amount	5 g
Quantity options	10 mg 100 mg 1 g 10 g 200 mg 25 mg 5 mg 50 mg 5 g
Category	Oncology Metabolism Diabetes Glucose Homeostasis Cholesterol & Lipid Metabolism Regulation of Appetite Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Skin Cancer Heart & Blood Cancer
Type	Inhibitors
Specific against	other
Smiles	CC1=C(C=C(C=C1)[N+](=O)[O-])S(=O)(=O)N(C)N=CC2=CN=C3N2C=C(C=C3)Br.Cl
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	372196-77-5'
Similar products	PIK-75
Available
Manufacturer - Targets	PI3K
Storage Conditions	2 years -80 in solvent
Molecular Weight	488, 74
Administration	Administered via i.p.
Animal Models	MTLn3 cells are injected into the right fourth mammary fat pad from the head of female severe-combined immunodeficient/NCr mice.
Cell lines	A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852 cells
Concentrations	0-10 uM
Dosages	<=1 uM
Formulation	PIK-75 is dissolved in DMSO and then diluted in PBS.
IC50	5.8 nM [1], 5.8 nM [1], 5.8 nM [1], 5.8 nM [1], 5.8 nM [1], 5.8 nM [1]
In vitro	PIK-75 shows the impressive potency and isoform selectivity at p110alpha while the corresponding IC50 values are 1300 nM, 76 nM and 510 nM for other PI3K isoforms, p110beta, -gamma, and -delta, respectively. Furthermore, when binding to purified p110alpha, PIK-75 is a noncompetitive inhibitor with respect to ATP with Ki of 36 nM and competitive with respect to the substrate PI with Ki of 2.3 nM. [1] PIK-75 also shows potent inhibition of DNA-PK. [2] PIK-75 (1 uM) reduces cell survival by significantly decreasing mitochondrial activity in unstimulated nonasthmatic airway smooth muscle (ASM) cells, asthmatic ASM cells, and lung fibroblasts. While in TGFbeta-stimulated ASM cells, PIK75 only decreases mitochondrial activity in asthmatic cells without effects in nonasthmatic cells. [3] A recent study shows that PIK-75 (10 nM) inhibits TNF-alpha-induced CD38 mRNA expression and significantly attenuates of TNF-alpha-induced ADP-ribosyl cyclase activity in human airway smooth muscle cells. [4]
In vivo	In the ErbB3WT tumor model, PIK-75 reduces in vitro chemotactic response to HRGbeta1 and lowers pAkt levels by 40%. Besides, PIK-75 significantly reduces tumor cell motility and in vivo invasion in ErbB3WT primary tumors. [5] In the CD1 male mice, PIK-75 leads to serious impairments in the, insulin tolerance test (ITT) and glucose tolerance test (GTT), and an increase in glucose production during a pyruvate tolerance test (PTT). [6]
Incubation Time	48 hours
Kinase Assay	Inhibition Assays, The PI3K inhibitor PIK-75 is dissolved at 10 mM in dimethyl sulfoxide and stored at 20C until use. PI3K enzyme activity is determined in 50 uL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 containing 180 uM phosphatidyl inositol, with the reaction started by the addition of 100 uM ATP (containing 2.5 uCi of [gamma-32P]ATP). After a 30-minute incubation at room temperature, the enzyme reaction is stopped by the addition of 50 uL of 1 M HCl. Phospholipids are then extracted with 100 uL of chloroform/methanol [1:1 (v/v)] and 250 uL 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 uL 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 uL of Kinase-Glo followed by a further 15-minute incubation. Luminescence is then read using a Fluostar plate reader. Results are analyzed using Prism.
Method	Mitochondrial activity is assessed after stimulation with TGFbeta 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 uL) into 24-well cluster plates prior to serial dilution (1:2) in duplicates. To each well, 100 uL of an appropriate MTT concentration (dissolved in PBS and filtered through a 0.2 um 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 uL of 10% sodium dodecyl sulfate (SDS) in 0.01 M HCl to each well. A sample (150 uL) 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.
Solubility (25C)	DMSO 3 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	PIK-75 HCl is a p110α inhibitor with IC50 of 5.8 nM (200-fold more potently than p110β), isoform-specific mutants at Ser773, and also potently inhibits DNA-PK with IC50 of 2 nM in cell-free assays.
Chemical Name	(E)-N'-((6-bromoH-imidazo[1, 2-a]pyridin-3-yl)methylene)-N, 2-dimethyl-5-nitrobenzenesulfonohydrazide hydrochloride
Features	PI3K and DNA-PK inhibitor

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

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S1205-5000-datasheet.pdf

S1205-5000-safety-datasheet.pdf