Discovery and structure - activity relationship studies of indole derivatives as liver X receptor (LXR) agonists

被引：8

作者：

Bakir, Farid

Kher, Sunil

Pannala, Madhavi

Wilson, Norma

Nguyen, Trang

Sircar, Ila

Takedomi, Kel

Fukushima, Chiaki

Zapf, James

Xu, Kui

Zhang, Shao-Hui

Liu, Juping

Morera, Lisa

Schneider, Lisa

Sakurai, Naoki

Jack, Rick

Cheng, Jie-Fei

机构：

[1] Tanabe Res Labs USA Inc, Dept Chem, San Diego, CA 92121 USA

[2] Tanabe Res Labs USA Inc, Dept Computat Discovery, San Diego, CA 92121 USA

[3] Tanabe Res Labs USA Inc, Dept Biol, San Diego, CA 92121 USA

[4] Tanabe Seiyaku Co Ltd, Dept Chem, Toda, Saitama, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 12期

关键词：

virtual screening; high-throughput gene profiling; LXR agonist; liver X receptor;

D O I：

10.1016/j.bmcl.2007.03.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3473 / 3479

页数：7

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