Docking Study of Biflavonoids, Allosteric Inhibitors of Protein Tyrosine Phosphatase 1B

다국어 초록 (Multilingual Abstract)

tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a
strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a
biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model
between amentoflavone and PTP1B was determined using automated docking study. Based on this docking
model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore
maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and
one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid
database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two
biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at
5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric
inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by
biflavonoids and give insights to develop potent inhibitors of PTP1B.

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