title: Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors.
abstract: Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compound library of licorice flavonoids allowed for the discovery of several compounds, including licoagrone (3), licoagrodin (4), licoagroaurone (5), and isobavachalcone (6), as new PTP1B inhibitors. It was revealed that these compounds inhibit the activity of PTP1B in different modes and with different selectivities and that they exhibit different cellular activity in the insulin-signaling pathway. Glycybenzofuran (1), a competitive PTP1B inhibitor, showed both excellent inhibitory selectivity against PTP1B and cellular activity on the insulin-stimulated Akt phosphorylation level. The similarity of its action profiling in the insulin-signaling pathway suggested its potential as a new anti-insulin-resistant drug candidate.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. Electronic address: liwei@phar.toho-u.ac.jp.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Songpei
authors.initials: S
authors.lastname: Li
authors.forename: Koji
authors.initials: K
authors.lastname: Higai
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Asada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
mesh_terms: D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D005419:Flavonoids; D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Flavonoids; Glycyrrhiza; Licorice; Protein tyrosine phosphatase 1B