Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta

Abstract

Protein tyrosine phosphatase 1B (PTP1B) appears to be an attractive target for the development of new drugs for type 2 diabetes and obesity. In our preliminary test, a MeOH extract of the stem barks of Sorbus commixta Hedl. (Rosaceae) showed strong PTP1B inhibitory activity. Bioassay−guided fractionation of the MeOH extract resulted in the isolation of two lupane−type triterpenes, lupenone (1) and lupeol (2). Compounds 1 and 2 inhibited PTP1B with IC₅₀ values of 13.7 ± 2.1 and 5.6 ± 0.9 μM, respectively. Kinetic studies revealed that both the compounds 1 and 2 are non−competitive inhibitors of PTP1B that decrease V_max values with no effect on K_m values.

Keywords::

• Protein tyrosine phosphatase 1B
• Sorbus commixta Hedl.
• Rosaceae
• lupenone
• lupeol
• non−competitive inhibitors

Declaration of interest: This work was supported partly by the Global Partnership Program (No. M60602000001-06E0200-00100) of Korea Foundation for International Cooperation of Science & Technology (KICOS) and KRIBB Research Initiative Program. The authors alone are responsible for the content and writing of the paper.