Journal: Cancers

Article Title: Regulation of Pleiotrophin and PTPRZ1 Expression by Hypoxia to Restrict Hypoxia-Induced Cell Migration.

doi: 10.3390/cancers17091516

Figure Lengend Snippet: Figure 6. The effect of PTPRZ1 expression on the hypoxia-induced endothelial cell proliferation and migration. (A) Ptprz1+/+ and Ptprz1−/−LMVECs were incubated for 24 h with 200 µM of DFX or 0.5 mM of DMOG and cell numbers were determined by direct counting. Results are expressed as the mean ± standard deviation (n = 3) of the % number of cells compared to the corresponding untreated cells (set by default as 100%). ns, non-significant. (B) Ptprz1+/+ and Ptprz1−/−LMVECs were incubated for 4 h with DFX or DMOG and migration was studied using the transwell assay. Results are expressed as the mean ± standard deviation (n ≥3) of the % number of cells compared to the corresponding untreated cells (set by default as 100%).

Article Snippet: To down-regulate PTPRZ1 expression, C6 cells or LNCaP cells at 60% confluency were incubated in a transfection medium (Santa Cruz Biotechnology Inc., #sc-36868) containing 80 nM annealed siRNA for PTPRZ1 [14,27] and siRNA transfection reagent (Santa Cruz Biotechnology Inc., #sc-29528) for 6 h. The medium was replaced with the corresponding full medium, and cells were cultured for 48 h before being used for further experiments.

Techniques: Expressing, Migration, Incubation, Standard Deviation, Transwell Assay

Journal: Cancers

Article Title: Regulation of Pleiotrophin and PTPRZ1 Expression by Hypoxia to Restrict Hypoxia-Induced Cell Migration.

doi: 10.3390/cancers17091516

Figure Lengend Snippet: Figure 7. A schematic representation of the effect of hypoxia on the PTN and PTPRZ1 expression in endothelial cells. Hypoxia activates HIFs and AP-1 to up-regulate the PTN expression in ανβ3 integrin-expressing cells to restrict the stimulatory effect of hypoxia on cell proliferation and migration. In cells that do not express αvβ3 integrin, hypoxia downregulates the PTN expression in a HIF- and AP-1-independent manner. In all cases, hypoxia upregulates the expression of PTPRZ1, which is known to negatively regulate ( ) HIF1α [41] and restricts hypoxia-induced cell migration.

Article Snippet: To down-regulate PTPRZ1 expression, C6 cells or LNCaP cells at 60% confluency were incubated in a transfection medium (Santa Cruz Biotechnology Inc., #sc-36868) containing 80 nM annealed siRNA for PTPRZ1 [14,27] and siRNA transfection reagent (Santa Cruz Biotechnology Inc., #sc-29528) for 6 h. The medium was replaced with the corresponding full medium, and cells were cultured for 48 h before being used for further experiments.

Techniques: Expressing, Migration

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Chemical structure of naloxegol, a PEGylated derivative of naloxol, which is derived from naloxone. The box encompasses the low molecular weight polyethylene glycol (PEG) chain that is covalently bound to the morphinan ring-based structure of naloxone.

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Derivative Assay, Molecular Weight

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Binding affinity of naloxegol to opioid receptor subtypes Data are mean ± S.E.M. values from 3 independent experiments.

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Binding Assay

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Competitive antagonism of naloxegol at the human µ -opioid receptor. The effects of 3 different concentrations of naloxegol (A) and methylnaltrexone (B) on morphine agonist concentration-response curves, as measured by guanosine 5- O -(3-[ 35 S]thio)triphosphate ([ 35 S]GTP γ S binding) (1 of 3 independent experiments) are shown. Each compound elicited a rightward shift in the morphine concentration-response curve with no reduction in E max .

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Concentration Assay, Binding Assay

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Naloxegol is a competitive neutral antagonist of morphine at the human µ -opioid receptor. This Schild plot depicts the effects of naloxegol (♦) and methylnaltrexone (▪) on morphine agonist concentration-response curves at the human µ -opioid receptor, as measured by [ 35 S]GTP γ S binding (pooled results of 3 independent experiments for each compound). Note the respective Schild slopes: –1.03 for naloxegol and –0.982 for methylnaltrexone. DR, dose ratio.

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Concentration Assay, Binding Assay

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Apparent permeability and efflux of naloxegol in the presence and absence of P-gp inhibitors, demonstrated by the Caco2 transport assay

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Permeability

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Comparative brain permeation of naloxegol in the rat Data are mean ± S.D.

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques:

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Quantitative whole body autoradiogram of sections through a male pigmented rat at 1 hour after the administration of a single oral dose of [ 14 C]naloxegol (50 mg/kg). Note the absence of radioactivity in the brain.

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Radioactivity

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Concentrations of radioactivity in selected tissues after administration of [ 14 C]naloxegol (50 mg/kg) to adult male and pregnant female rats

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Radioactivity, Concentration Assay

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: Pharmacologic Profile of Naloxegol, a Peripherally Acting µ -Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

doi: 10.1124/jpet.116.239061

Figure Lengend Snippet: Predicted plasma concentration-time profile for oral naloxegol 25 mg. At this maximum clinically approved dose, naloxegol exposure is predicted to be insufficient to antagonize the δ -opioid receptor. The light blue area represents the 90% confidence interval ( N = 500 simulations from phase 3 studies).

Article Snippet: 14 C-radiolabeled naloxegol [1.0 mCi/ml; specific activity 49.5 mCi/mmol (2.80 MBq/mg); Isotope Chemistry, AstraZeneca] was stored at –20°C in the dark.

Techniques: Clinical Proteomics, Concentration Assay