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. 2014 Sep 29;5(5):1000232.
doi: 10.4172/2155-9562.1000232.

4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol) (CNB-001) Does Not Regulate Human Recombinant Protein-Tyrosine Phosphatase1B (PTP1B) Activity in vitro

Paul A Lapchak  1 , Jacqueline A Lara  2 , Paul D Boitano  2
Affiliations

4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol) (CNB-001) Does Not Regulate Human Recombinant Protein-Tyrosine Phosphatase1B (PTP1B) Activity in vitro

Paul A Lapchak et al. J Neurol Neurophysiol. .

Abstract

Protein-Tyrosine Phosphatase1B (PTP1B) is a negative regulator of the insulin signaling pathway and is a potential therapeutic target for treatment of type 2 diabetes, cardiovascular disease, metabolic syndrome and cancer. It has been postulated that CNB-001 [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol)] may regulate PTP1B activity suggested by a computer-based active site docking recognition model. This possibility was studied using a human recombinant PTP1B assay, and a phospho-peptide fragment of the insulin receptor β subunit domain (IR5). The positive control, suramin, inhibited PTP1B with an IC50 (half minimal (50%) inhibitory concentration) value of 16.34 µM; CNB-001 did not affect enzyme activity across the range of 1nM-0.1mM. This study suggests that PTP1B inhibition is not involved in the beneficial effects of CNB-001 in obese type 2 diabetic mice.

Keywords: Curcumin analog; Metabolic disorder; Neuroprotection; Neurotrophic; Phosphatases; Pleiotropic.

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Figures

Figure 1
Figure 1
Suramin inhibits PTP1B with an IC50 of 16.34 µM; PTP1B assays were run in triplicate with either buffer or suramin (0.1mM–1nM). Significantly different (***p<0.01) from baseline enzyme activity levels measured by phosphate product produced over 30 minutes. IC50 value is calculated inhibitory concentration required for 50% enzyme activity inhibition compared to baseline control. Paired-t-test was used for statistical analysis (Graph Pad Inc.).
Figure 2
Figure 2
CNB-001 does not affect PTP1B activity in vitro; PTP1B assays were run in triplicate with either DMSO of CNB-001 (0.1mM–1nM). Activity measured in the presence of CNB-001 was not significantly different (p>0.05) from baseline enzyme activity levels measured by phosphate product produced over 30 minutes. Baseline was lowered by the presence of DMSO in the assay. Paired-t-test was used for statistical analysis (Graph Pad Inc.).
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References

    1. Lapchak PA, McKim JM., Jr CeeToxTm Analysis of CNB-001 a Novel Curcumin-Based Neurotrophic/Neuroprotective Lead Compound to Treat Stroke: Comparison with NXY-059 and Radicut. Transl Stroke Res. 2011;2:51–59. - PMC - PubMed
    1. Lapchak PA. Neuroprotective and neurotrophiccurcuminoids to treat stroke: a translational perspective. Expert Opin Investig Drugs. 2011;20:13–22. - PubMed
    1. Lapchak PA, Schubert DR, Maher PA. Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke. J Neurochem. 2011;116:122–131. - PMC - PubMed
    1. Valera E, Dargusch R, Maher PA, Schubert D. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease. J Neurosci. 2013;33:10512–10525. - PMC - PubMed
    1. Liu Y, Dargusch R, Maher P, Schubert D. A broadly neuroprotective derivative of curcumin. J Neurochem. 2008;105:1336–1345. - PubMed

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