Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta.
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.
Na
Minkyun
M
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea.
Kim
Bo Yeon
BY
Osada
Hiroyuki
H
Ahn
Jong Seog
JS
D001667:Binding, Competitive; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry*; D018547:Plant Stems / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D031994:Sorbus / Q000737:chemistry*; D014315:Triterpenes / Q000494:pharmacology*; D000094042:Lupanes
D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D014315:Triterpenes; C470592:lupenone; D000094042:Lupanes; C010480:lupeol