Peroxisome proliferator-activated receptor modulator

Ram, V.J. (2003) Therapeutic significance of peroxisome proliferator-activated receptor modulators in diabetes. Drugs Today, 39, 609-632. 

Schupp, M., Clemenz, M., Gineste, R., Witt, H., Janke, J., Helleboid, S., Hennuer, N., Ruiz, P., Unger, T., Staels, B., and Kintscher, U. (2005). Molecular characterization of new selective peroxisome proliferator-activated receptor y modulators with angiotensin receptor blocking activity. Diabetes 54, 3442-3452. 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

Netoglitazone is an insulin sensitizer currently in Phase II clinical trials. It is able to modulate both PPAR-a and PPAR-y subtypes of peroxisome proliferator-activated receptor (Phase ll). Metaglidasen (MBX-102) is the (—)-enantiomer of the NSAID halofenate. This selective PPAR-y nuclear receptor agonist is being evaluated (Phase II) as an insulin sensitizer. It is structurally different from the currently marketed glitazones (Figure 8.84). ... 

Hepatic and peripheral effects of fibrates. These effects are mediated by activation of peroxisome proliferator-activated receptor-a, which modulates the expression of several proteins. LPL, lipoprotein lipase VLDL, very-low-density lipoproteins. 

Park EY, Cho IJ, Kim SG. Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer. Cancer Res 2004 64 3701-3713. 

The activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of A(f from the brain of a transgenic mouse model of AD, with increased expression of ApoE and its main transporters. Both a PPARy agonist (ciplitazone) and a PPARa agonist (WT 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR-based therapy could act simultaneously in different cellular components [437]. 

Peroxisome proliferator-activated receptor (PPAR) y and PPARra agonists modulate mitochondrial fusion-fission dynamics Relevance to reactive oxygen species (ROS)-related neurodegenerative disorders PLoS One 8 e64019. doi 10.1371/journal.pone. 0064019... 

Pasceri V, Wu HD, Willerson IT, et al. (2000) Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 10 235—238... 

Thiazolidinediones are another class of heterocyclic carboxylic acid surrogates commonly used for peroxisome proliferator-activated receptors (PPAR) agonists, as potent antihyperglycemic and lipid activity modulators. Other interesting, but less studied heterocyclic surrogates are 3,5-dioxo-l,2,4-oxadiazohdine, 3-hydroxy-1,2,5-thiadiazoles, l,2,4-oxadiazole-5(4//)-ones, 1,2,4-thiadi-azole-5(4H)-ones , 3,5-difluoro-4-hydroxyphenyl, and 3 -hydroxy-7-pyrones. ... 

Peroxisome Proliferator-Activated Receptor 7 Modulation for the Treatment of Type 2 Diabetes... 

Halofenate is a selective peroxisome proliferator-activated receptor y modulator with antidiabetic activity. Diabetes, 55, 2523-2533. 

Mukherjee, R., Hoener, P.A., Jow, L. et al. (2000) A selective peroxisome proliferator-activated receptor y (PPARy) modulator blocks adipocyte differentiation but... 

Peroxisome proliferator-activated receptors are ligand-activated receptors which regulate a number of genes involved in nutrient metabolism and energy homeostasis, and thus have served as drug targets for the treatment of metabolic diseases. Anne Reifel Miller and Alan M. Warshawsky review peroxisome proliferator-activated receptor y modulation for the treatment of type 2 diabetes. 

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