Paul A Lapchak, Jacqueline A Lara and Paul D Boitano
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.