2013 Fiscal Year Final Research Report
Discovery of novel natural PTP1B inhibitors as antidiabetes drug seeds
| Project/Area Number |
23790025
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemical pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
LI Wei 東邦大学, 薬学部, 准教授 (90328633)
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| Project Period (FY) |
2011 – 2013
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| Keywords | プロテインチロシンホスファターゼ1B阻害剤 / 糖尿病 / 天然物 / 創薬 |
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| Research Abstract |
Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes. Screening of plant extracts and natural compounds libraries led to the discovery of novel PTP1B inhibitors originated from natural sources, exemplified by glycybenzofuran from Glycyrrhiza uralensis, and picrasidine L from Picrasma quassioides, which were demonstrated to be competitive PTP1B inhibitors by kinetic analyses, exhibited excellent inhibitory selectivities against homologous protein tyrosine phosphatases. Glycybenzofuran and picrasidine L also exhibited cellular activity in the insulin-signaling pathway by increasing the insulin-stimulated Akt phosphorylation level in human hepatocellular liver carcinoma HepG2 cells, suggesting their potential for new anti-insulin-resistant drug developments.
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