Abstract
Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization.
Keywords:
Insulin-sensitizing effect; PTP1B; Structure–activity relationships; Type 2 diabetes mellitus; Varic acid.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / drug effects
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Depsides / chemistry
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Depsides / isolation & purification
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Depsides / pharmacology*
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Fungi / chemistry*
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Humans
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Mice
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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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Blood Glucose
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Depsides
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Enzyme Inhibitors
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trivaric acid
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PTPN1 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1