Structure-based virtual screening approach to identify novel classes of PTP1B inhibitors

被引：41

作者：

Park, Hwangseo ^{[2
]}

Bhattarai, Bharat Raj ^{[3
,4
]}

Ham, Seung Wook ^{[1
]}

Cho, Hyeongjin ^{[3
,4
]}

机构：

[1] Chung Ang Univ, Dept Chem, Seoul 156756, South Korea

[2] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea

[3] Inha Univ, Dept Chem, Inchon 402751, South Korea

[4] Inha Univ, Inst Mol Cell Biol, Inchon 402751, South Korea

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 08期

关键词：

Protein tyrosine phosphatase 1B; PTP1B; Structure-activity relationship; Virtual screening; TYROSINE-PHOSPHATASE; 1B; INSULIN SENSITIVITY; GENETIC ALGORITHM; PROTEIN; SOLVATION; DOCKING; MICE; THERAPEUTICS; RESISTANCE; ADIPOSITY;

D O I：

10.1016/j.ejmech.2009.02.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Discovery of protein tyrosine phosphatase 1 B (PTP1B) inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type 2 diabetes and obesity. We have been able to identify 9 novel PTP1B inhibitors by means of a computer-aided drug design protocol involving virtual screening with docking simulations under consideration of the effects of ligand solvation in the binding free energy function. Because the newly discovered inhibitors are structurally diverse and reveal a significant potency with IC50 values lower than 50 mu M, all of them can be considered for further development by structure-activity relationship studies. Structural features relevant to the interactions of the newly identified inhibitors with the active-site residues of PTP1B are discussed in detail. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：3280 / 3284

页数：5

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