Journal
MOLECULAR PHARMACOLOGY
Volume 73, Issue 5, Pages 1434-1443Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/mol.107.042689
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Funding
- NIA NIH HHS [R01-AG027713-02] Funding Source: Medline
- Telethon [GGP07063] Funding Source: Medline
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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.
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