Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents

被引：39

作者：

Beck, Hilary P. ^{[1
]}

Kohn, Todd ^{[1
]}

Rubenstein, Steven ^{[1
]}

Hedberg, Christine ^{[1
]}

Schwandner, Ralf ^{[2
]}

Hasslinger, Kerstin ^{[2
]}

Dai, Kang ^{[1
]}

Li, Cong ^{[1
]}

Liang, Lingining ^{[1
]}

Wesche, Holger ^{[1
]}

Frank, Brendon ^{[1
]}

An, Songhzu ^{[1
]}

Wckramasinghe, Dineli ^{[1
]}

Jaen, Juan ^{[1
]}

Medina, Julio ^{[1
]}

Hungate, Randall ^{[1
]}

Shen, Wang ^{[1
]}

机构：

[1] Amgen Inc, Chem Res & Discovery, San Francisco, CA 94080 USA

[2] Amgen Res GmbH, Chem Res & Discovery, Regensburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 03期

关键词：

LPA2; EDG4; LPA; anticancer agents;

D O I：

10.1016/j.bmcl.2007.12.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The LPA(2) protein is overexpressed in many tumor cells. We report the optimization of a series of LPA(2) antagonists using calcium mobilization assay (aequorin assay) that led to the discovery of the first reported inhibitors selective for LPA(2). Key compounds were evaluated in vitro for inhibition of LPA(2) mediated Erk activation and proliferation of HCT-116 cells. These compounds could be used to evaluate the benefits of LPA(2) inhibition both in vitro and in vivo. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1037 / 1041

页数：5

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