Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from <i>Sorbus commixta</i>

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 IC(50) values of 13.7 +/- 2.1 and 5.6 +/- 0.9 microM, 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.