In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886)

被引：28

作者：

Biserni, Andrea ^{[1
,2
]}

Giannessi, Fabio ^{[3
]}

Sciarroni, Anna Floriana ^{[3
]}

Milazzo, Ferdinando Maria ^{[3
]}

Maggi, Adriana ^{[1
]}

Ciana, Paolo ^{[1
]}

机构：

[1] Univ Milan, Dept Pharmacol Sci, Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy

[2] Transgen Operat Prod srl, Lodi, Italy

[3] Sigma Tau Ind Farmaceut Riunite SpA, Dept Endocrinol & Metab, Pomezia, Italy

来源：

MOLECULAR PHARMACOLOGY | 2008年 / 73卷 / 05期

关键词：

D O I：

10.1124/mol.107.042689

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We report here the finding of a new pharmacological activity of a well known antagonist of peroxisome proliferator-activated receptors (PPARs). PPARs belong to the family of nuclear receptors playing a relevant role in mammalian physiology and are currently believed to represent a major target for the development of innovative drugs for metabolic and inflammatory diseases. In the present study, the application of reporter animal technology was instrumental to obtain the global pharmacological profiling indispensable to unraveling 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886)-selective PPAR modulator (SPPARM) activity not underlined by previous traditional, cell-based studies. The results of this study, demonstrating the usefulness of reporter mice, may open new avenues for the development of innovative drugs for cardiovascular, endocrine, neural, and skeletal systems characterized by limited side effects.

引用

页码：1434 / 1443

页数：10

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