Methylenedisalicylic acid derivatives: new PTP1B inhibitors that confer resistance to diet-induced obesity.
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.
Shrestha
Suja
S
Department of Chemistry and Institute of Molecular Cell Biology, Inha University, 253 Yonghyun-dong, Nam-ku, Incheon 402-751, Republic of Korea.
Bhattarai
Bharat Raj
BR
Chang
Kyung Ja
KJ
Lee
Keun-Hyeung
KH
Cho
Hyeongjin
H
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D004032:Diet; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D012459:Salicylates / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
D019440:Anti-Obesity Agents; D012459:Salicylates; C026816:5,5'-methylenedisalicylic acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse