Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors

被引：10

作者：

Choi, Hwanho ^{[1
]}

Park, Ho Jeong ^{[2
]}

Shin, Jong Chul ^{[2
]}

Ko, Hyun Sun ^{[2
]}

Lee, Jung Kyun ^{[3
]}

Lee, Soyoung ^{[4
]}

Park, Hwangseo ^{[1
]}

Hong, Sungwoo ^{[4
]}

机构：

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

[2] Catholic Univ, Coll Med, Seoul St Marys Hosp, Dept Obstet & Gynecol, Seoul 137040, South Korea

[3] Soomshinun Oriental Med Clin, Yongin 448170, Gyeonggi Do, South Korea

[4] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Virtual screening; Docking; p38; MAPK; Inhibitor; Anti-inflammatory agents; GENETIC ALGORITHM; PROTEIN-KINASE; POTENT; SOLVATION; DOCKING; IDENTIFICATION; DESIGN;

D O I：

10.1016/j.bmcl.2012.01.104

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38 alpha MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC50 values ranging from 0.7 to 20 mu M. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2195 / 2199

页数：5

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