- Functional and Structural Insights into Human PPARα/δ/Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate
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Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment.
- Akahane, Makoto,Habu, Yuki,Honda, Akihiro,Ishii, Isao,Kamata, Shotaro,Kaneko, Chihiro,Machida, Yui,Miyawaki, Saeka,Oyama, Takuji,Shiiyama, Yui,Uchii, Kie
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- Double emulsion techniques for making novel compositions containing gluten and polysaccharides that contain uronic acid residues useful for encapsulating fats, oils and solids
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Method of making compositions comprising gluten and polysaccharides that contain uronic acid residues encapsulating fats, oils and solids comprising double emulsion techniques.
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- Compositions containing gluten and polysaccharides that contain uronic acid residues useful for encapsulating fats, oils and solids
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The present invention relates to compositions useful for encapsulating fats, oils or solids, comprising gluten and polysaccharides that contains uronic acid residues.
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- Pesticidal concentrate compositions
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A pesticidal concentrate comprising a pesticidal component suspended in an oily component, the composition comprising 1-55% by weight of pesticide, 20-90% by weight of the oily component and 1-45% by weight of a surfactant component, and optionally water and optionally filler, the surfactant component comprising one or more stabilizing constituents comprising a C5-30 hydrocarbylene chain carrying a group capable of forming hydrogen bonds with water, and optionally one or more other constituents selected from the group consisting of non-ionic and ionic surfactants, the stabilizing constituent being present in an amount of at least 4% by weight, calculated on the total amount of surfactant component in the composition. Examples of stabilizing constituents are fatty alcohols and amino group-containing surfactants, especially ampholytes. Pesticidal concentrate compositions comprising 1-55% by weight of finely ground dithiocarbamate or glyphosate suspended in 10-90% by weight of an oily component and comprising 1-50% by weight of a surfactant component, calculated on the total composition, may be prepared. The pesticidal concentrate compositions are used in the preparation of ready-to-use-spray liquid, normally comprising 0.1-10% of concentrate and 90-99.9% of water.
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- Process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and their alkali metal salts
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Process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and the alkali metal salts thereof by adding a double molar amount of an aqueous alkali hydroxide to a boiling mixture of a (benzyl- or phenoxy-)-phenol and 2-chloropropionic acid
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- Herbicidal esters of D-1-(phenoxy-4-phenoxy)propionic acid
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Optically active enantiomers of the formula I STR1 where R is a group of the formulae STR2 R1 and R2, among others, are halogen or CF3 and Z is a carboxyl, carboxylate, carboxylic acid ester, thioester, carbonamide, carboxylic acid anilide, carbohydrazide or thioamide group, are interesting herbicides the effect of which is considerably superior to that of the optically inactive racemates.
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- 2-[P-(p-Substituted phenoxy)phenoxy]propionyl oximes
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2-[p-(p-substituted phenoxy)phenoxy] propionyl oximes, processes for their preparation, herbicidal compositions containing these oximes and methods of use of the herbicidal compositions are disclosed.
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- HCG 004, a new highly potent hypolipidaemic drug
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In normolipidemic and hyperlipidemic animals 2 [4(4' chlorophenoxy) phenoxy] propionic acid (HCG 004) is a well tolerated and highly effective oral hypolipidemic drug. Within the hypolipidemically interesting dosage range no other pharmacological or chronic toxicological effects were found contraindicating the therapeutic use in humans.
- Granzer,Nahm
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p. 1353 - 1354
(2007/10/06)
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