Abstract
Methylenedisalicylic acid derivatives were synthesized and their inhibitory activities against protein tyrosine phosphatases (PTPases) examined. Two of the compounds, 8 and 9, showed K(i) values of 9.4 and 6.3microM against PTP1B, 4- and 7-fold lower values compared to those against TC-PTP. They were reversible and slow-binding inhibitors against PTP1B. When compound 8 was fed to a mouse model, the weight gain and adipocyte fat storage induced by a high-fat-diet were significantly suppressed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / drug effects
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Adipocytes / physiology
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Animals
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Anti-Obesity Agents / chemical synthesis
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Anti-Obesity Agents / pharmacology
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Anti-Obesity Agents / therapeutic use*
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Diet
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Disease Models, Animal
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Mice
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Mice, Inbred C57BL
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Obesity / prevention & control*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Salicylates / chemical synthesis
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Salicylates / pharmacology
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Salicylates / therapeutic use*
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Weight Gain / drug effects
Substances
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Anti-Obesity Agents
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Salicylates
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5,5'-methylenedisalicylic acid
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases
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Ptpn1 protein, mouse