N-acylthiadiazolines, a new class of liver x receptor agonists with selectivity for LXRβ

被引：51

作者：

Molteni, Valentina

Li, Xiaolin

Nabakka, Juliet

Liang, Fang

Wityak, John

Koder, Alan

Vargas, Leo

Romeo, Russell

Mitro, Nico

Mak, Puiying A.

Seidel, Martin

Haslam, Jennifer A.

Chow, Donald

Tuntland, Tove

Spalding, Tracy A.

Brock, Ansgar

Bradley, Michelle

Castrillo, Antonio

Tontonoz, Peter

Saez, Enrique

机构：

[1] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

[3] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Lab Med, Los Angeles, CA 90095 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 17期

关键词：

D O I：

10.1021/jm070453f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have identified a novel liver X receptor (LXR) agonist (2) that activates the LXR beta subtype with selectivity over LXR alpha. LXR beta selectivity was confirmed using macrophages derived from LXR mutant mice. Despite its selectivity and modest potency, the compound can induce APO-AI-dependent cholesterol efflux from macrophages with full efficacy. Our results indicate that it is possible to achieve significant LXR beta selectivity in a small molecule while maintaining functional LXR activity.

引用

收藏

页码：4255 / 4259

页数：5

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