title: 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) Activityin vitro.
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.
authors.affiliation: Department of Neurology, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, USA ; Department of Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lapchak
authors.affiliation: Department of Neurology, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Lara
authors.affiliation: Department of Neurology, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Boitano
keywords: Curcumin analog; Metabolic disorder; Neuroprotection; Neurotrophic; Phosphatases; Pleiotropic