Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode

被引：35

作者：

Meyers, Marvin J. ^{[1
]}

Pelc, Matthew ^{[1
]}

Kamtekar, Satwik ^{[1
]}

Day, Jacqueline ^{[1
]}

Poda, Gennadiy I. ^{[1
]}

Hall, Molly K. ^{[1
]}

Michener, Marshall L. ^{[1
]}

Reitz, Beverly A. ^{[1
]}

Mathis, Karl J. ^{[1
]}

Pierce, Betsy S. ^{[1
]}

Parikh, Mihir D. ^{[1
]}

Mischke, Deborah A. ^{[1
]}

Long, Scott A. ^{[1
]}

Parlow, John J. ^{[1
]}

Anderson, David R. ^{[1
]}

Thorarensen, Atli ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, St Louis Labs, Chesterfield, MO 63017 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期

关键词：

cFMS; CSF-1R; Kinase; DFG-in; DFG-out; Structure-based drug design; BIOCHEMICAL-MECHANISMS; CFMS; EFFICIENCY; MACROPHAGE; DISCOVERY;

D O I：

10.1016/j.bmcl.2010.01.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1543 / 1547

页数：5

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