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WY-14643, also known as Pirinixic Acid, has an agonistic action as peroxisome proliferator-activated receptor (PPAR). It is shown that aliphatic α-substitution of WY-14643 enhances both PPARα and PPARγ agonism. It has been demonstrated that aliphatic substitution in a-position to the carboxylic acid head group of WY-14643 improves both PPARa and PPARg activity and leads to balanced dual PPARa/g agonists in the lower micromolar range, with a-hexyl pirinixic acid as the most active compound. WY-14,643 can moderately elevate the level of TNFa mRNA in the liver. WY-14,643 stimulates production of low levels of hepatic TNFα by Kupffer cells which acts indirectly as a hepatocyte mitogen

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