Recent advances in Liver X Receptor biology and chemistry

被引：26

作者：

Goodwin, Bryan J. ^{[1
]}

Zuercher, William J. ^{[1
]}

Collins, Jon L. ^{[1
]}

机构：

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

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2008年 / 8卷 / 09期

关键词：

Liver X Receptors; LXR chemotypes; LXR crystal structure; LXR therapeutic indications;

D O I：

10.2174/156802608784535075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The Liver X Receptors LXR alpha and LXR beta are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Seminal studies with genetic and chemical tools were instrumental in the elucidation of cholesterol metabolism, gluconeogenesis, inflammation, and lipogenesis as signaling pathways that are controlled by the LXRs. First generation non-steroidal LXR agonists show beneficial effects in multiple animals models of human disease yet have not progressed in the clinic due to deleterious side effects in the liver. Numerous reports have appeared in the the recent literature that disclose new LXR signaling pathways and the identication of novel LXR chemotypes that may show improved therapeutic indices. This review will provide a brief historical perspective but will primarily focus on recent advances in LXR biology and chemistry.

引用

页码：781 / 791

页数：11

共 101 条

[1] Inactivation of liver X receptor β leads to adult-onset motor neuron degeneration in male mice [J].

Andersson, S ;

Gustafsson, N ;

Warner, M ;

Gustafsson, JÅ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) :3857-3862

[2] Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans - No alteration in adipose tissue of obese and NIDDM patients [J].

Auboeuf, D ;

Rieusset, J ;

Fajas, L ;

Vallier, P ;

Frering, V ;

Riou, JP ;

Staels, P ;

Auwerx, J ;

Laville, M ;

Vidal, H .

DIABETES, 1997, 46 (08) :1319-1327

[3]

Auwerx J, 1999, CELL, V97, P161

[4] An update on non-steroidal liver X receptor agonists and their potential use in the treatment of atherosclerosis [J].

Bennett, D. Jonathan ;

D Brown, Lindsay ;

Cooke, Andrew J. ;

Edwards, Andrew S. .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2006, 16 (12) :1673-1699

[5] Identification of a subtype selective human PPARα agonist through parallel-array synthesis [J].

Brown, PJ ;

Stuart, LW ;

Hurley, KP ;

Lewis, MC ;

Winegar, DA ;

Wilson, JG ;

Wilkinson, WO ;

Ittoop, OR ;

Willson, TM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (09) :1225-1227

[6] The effects of ABCA1 on cholesterol efflux and Aβ levels in vitro and in vivo [J].

Burns, Mark P. ;

Vardanian, Lilit ;

Pajoohesh-Ganji, Ahdeah ;

Wang, Lili ;

Cooper, Matthew ;

Harris, Donnie C. ;

Duff, Karen ;

Rebeck, G. William .

JOURNAL OF NEUROCHEMISTRY, 2006, 98 (03) :792-800

[7]

BUSCH BB, 2007, Patent No. 2007002559

[8] Antidiabetic action of a liver X receptor agonist mediated by inhibition of hepatic gluconeogenesis [J].

Cao, GQ ;

Liang, Y ;

Broderick, CL ;

Oldham, BA ;

Beyer, TP ;

Schmidt, RJ ;

Zhang, YY ;

Stayrook, KR ;

Suen, C ;

Otto, KA ;

Miller, AR ;

Dai, JN ;

Foxworthy, P ;

Gao, H ;

Ryan, TP ;

Jiang, XC ;

Burris, TP ;

Eacho, PI ;

Etgen, GJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (02) :1131-1136

[9] Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis [J].

Carstea, ED ;

Morris, JA ;

Coleman, KG ;

Loftus, SK ;

Zhang, D ;

Cummings, C ;

Gu, J ;

Rosenfeld, MA ;

Pavan, WJ ;

Krizman, DB ;

Nagle, J ;

Polymeropoulos, MH ;

Sturley, SL ;

Ioannou, YA ;

Higgins, ME ;

Comly, M ;

Cooney, A ;

Brown, A ;

Kaneski, CR ;

BlanchetteMackie, EJ ;

Dwyer, NK ;

Neufeld, EB ;

Chang, TY ;

Liscum, L ;

Strauss, JF ;

Ohno, K ;

Zeigler, M ;

Carmi, R ;

Sokol, J ;

Markie, D ;

ONeill, RR ;

vanDiggelen, OP ;

Elleder, M ;

Patterson, MC ;

Brady, RO ;

Vanier, MT ;

Pentchev, PG ;

Tagle, DA .

SCIENCE, 1997, 277 (5323) :228-231

[10] Insulin regulation of phosphoenolpyruvate carboxykinase-C gene transcription: The role of sterol regulatory element-binding protein 1c [J].

Chakravarty, Kaushik ;

Hanson, Richard W. .

NUTRITION REVIEWS, 2007, 65 (06) :S47-S56

← 1 2 3 4 5 6 7 8 9 10 →