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ID: ALA1151785

Journal: Bioorg Med Chem

Title: Oleanolic acid and its derivatives: new inhibitor of protein tyrosine phosphatase 1B with cellular activities.

Authors: Zhang YN, Zhang W, Hong D, Shi L, Shen Q, Li JY, Li J, Hu LH.

Abstract: Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13 with a K(i) of 130 nM, which exhibited good selectivity between other phosphatases involved in insulin pathway except T-cell protein tyrosine phosphatase. Further evaluation in cell models illustrated that the derivatives enhanced insulin receptor phosphorylation in CHO/hIR cells and also stimulated glucose uptake in L6 myotubes with or addition of without insulin.

CiteXplore: 18707891

DOI: 10.1016/j.bmc.2008.07.080