Abstract
A series of 5,7-dihydroxyflavanone derivatives were synthesized and identified as reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with IC50 values in the micromolar range. Compound 4k had the most potent in vitro inhibition activity against PTP1B (IC50 = 2.37 ± 0.37 μM) and the greatest selectivity (3.7-fold) for PTP1B relative to T-cell protein tyrosine phosphatase. Cell-based studies revealed that 4k was membrane-permeable and enhanced insulin receptor tyrosine phosphorylation in CHO/hIR cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetulus
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Flavanones / chemical synthesis
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Flavanones / chemistry*
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Flavanones / pharmacology*
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Humans
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Models, Molecular
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Molecular Structure
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Flavanones
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pinocembrin
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Protein Tyrosine Phosphatase, Non-Receptor Type 1