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 Ki values of 9.4 and 6.3 μM 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.

Graphical abstractCompound 8 inhibited PTP1B in vitro and suppressed diet-induced weight gain in mice.Figure optionsDownload full-size imageDownload as PowerPoint slide