China Raw Material Strong Leavening Sugar GW0742 Powder For Obesity Treatment 317318-84-6

China Raw Material Strong Leavening Sugar GW0742 Powder For Obesity Treatment 317318-84-6

GW0742 Basic Info:

GW0742, also known as GW610742, is a PPARδ/β agonist. GW0742 Induces Early Neuronal Maturation of Cortical Post-Mitotic Neurons. GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity. GW0742 has direct protective effects on right heart hypertrophy.GW0742 may enhance lipid metabolism in heart both in vivo and in vitro.

GW0742 (GW610742) is a potent and highly selective PPARδ agonist. EC50 values are 1nM, 1.1μM and 2 μM for transactivation of human PPARδ, -α, and -γ receptors respectively. IC50 value: 1nM, 1.1μM and 2 μM (EC50, for PPARδ, -α, and -γ) Target: PPAR in vivo: GW0742 is a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Data showed that GW0742-treatment (0.3 mg/Kg, 10 percent DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of:

1) cytokine production;
2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity;
3) IkBα degradation and NF-kB nuclear translocation;
4) ERK phosphorylation;
5) stress oxidative by NO formation due to iNOS expression;
6) nitrotyrosine and PAR localization;
7) the degree of apoptosis, evaluated by Bax and Bcl-2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO--instillation in mice.

GW0742 Application:

GW 0742 activates AMP-activated protein kinase and stimulates glucose uptake in skeletal muscle tissue , and GW 501516 has been demonstrated to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome , most likely by stimulating fatty acid oxidation .

GW0742 has been proposed as a potential treatment for obesity and related conditions , especially when used in conjunction with a synergistic compound AICAR , as the combination has been shown to significantly increase exercise endurance in human.

How GW0742 Works:

The highest antagonist activity for GW0742 was found for VDR and the androgen receptor (AR). Surprisingly, GW0742 behaved as PPAR agonist/antagonist activating transcription at lower concentration and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742+ increased fluorescence intensity and fluorescence polarization at an excitation wavelength of 595 nm and emission wavelength of 615 nm in a dose dependent manner.

The GW0742-inhibited NR-coactivator binding resulted in a reduced expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3 and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.

GW0742 / GW610742 Biological Activity:

GW0742 / GW610742 is a potent and highly selective PPARδ agonist. EC50 values are 1nM, 1.1μM and 2 μM for transactivation of human PPARδ, -α, and -γ receptors respectively.

GW0742 is a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10 percent DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of:cytokine production; leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; IkBα degradation and NF-kB nuclear translocation; ERK phosphorylation; stress oxidative by NO formation due to iNOS expression; nitrotyrosine and PAR localization; the degree of apoptosis, evaluated by Bax and Bcl-2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO--instillation in mice.

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