Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure

被引：40

作者：

Jaye, MC ^{[1
]}

Krawiec, JA ^{[1
]}

Campobasso, N ^{[1
]}

Smallwood, A ^{[1
]}

Qiu, CY ^{[1
]}

Lu, Q ^{[1
]}

Kerrigan, JJ ^{[1
]}

Alvaro, MDL ^{[1
]}

Laffitte, B ^{[1
]}

Liu, WS ^{[1
]}

Marino, JP ^{[1
]}

Meyer, CR ^{[1
]}

Nichols, JA ^{[1
]}

Parks, DJ ^{[1
]}

Perez, P ^{[1
]}

Sarov-Blat, L ^{[1
]}

Seepersaud, SD ^{[1
]}

Steplewski, KM ^{[1
]}

Thompson, SK ^{[1
]}

Wang, P ^{[1
]}

Watson, MA ^{[1
]}

Webb, CL ^{[1
]}

Haigh, D ^{[1
]}

Caravella, JA ^{[1
]}

Macphee, CH ^{[1
]}

Willson, TM ^{[1
]}

Collins, JL ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 17期

关键词：

D O I：

10.1021/jm050532w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 (4) as an LXR ligand. 4 recruits the steroid receptor coactivator-1 to human LXR alpha and LXRP with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.

引用

页码：5419 / 5422

页数：4

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