title: Development of an automated protein-tyrosine phosphatase 1B inhibition assay and the screening of putative insulin-enhancing vanadium(IV) and zinc(II) complexes.
abstract: The inhibition of protein-tyrosine phosphatase 1B (PTP1B) is a potential target for treatment of type 2 diabetes. Vanadium and zinc metal coordinated complexes have insulin-enhancing activities, and while vanadium compounds inhibit PTP1B, little is known on the mode of action of zinc compounds. In this study we developed an automated PTP1B inhibition assay that allows for a rapid assessment of the PTP1B inhibition strength of candidate compounds. Synthetic vanadium(IV) and zinc(II) complexes were evaluated: IC50 values for vanadium complexes ranged from 0.06 to 0.8 microM whereas for zinc compounds, values were above 10 microM. Vanadium sulfate, a non-conjugated inorganic salt, had stronger inhibition activity than any of the conjugated metal complexes.
authors.affiliation: Proteonik Inc., Gyeonggi Technopark, Rm 911, 1271-11, Sangnok-Gu, Ansan, 425-170, Korea. seale@preoteonik.com
authors.forename: Andre P
authors.initials: AP
authors.lastname: Seale
authors.forename: Lucia A
authors.initials: LA
authors.lastname: de Jesus
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Yeon-Hong
authors.initials: YH
authors.lastname: Choi
authors.forename: H B
authors.initials: HB
authors.lastname: Lim
authors.forename: Cheong-Soo
authors.initials: CS
authors.lastname: Hwang
authors.forename: Yang-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry; D007328:Insulin / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000032:analysis* / Q000037:antagonists & inhibitors*; D012371:Robotics / Q000379:methods*; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014639:Vanadium / Q000032:analysis / Q000737:chemistry*; D015032:Zinc / Q000032:analysis / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D014639:Vanadium; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D015032:Zinc