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• W2057921652 abstract "Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylascochlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3H10T1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-O-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors." @default.
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• W2057921652 date "2003-08-19" @default.
• W2057921652 modified "2023-10-09" @default.
• W2057921652 title "Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors" @default.
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• W2057921652 doi "https://doi.org/10.1021/jm0205649" @default.
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• W2057921652 hasPublicationYear "2003" @default.
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