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Herein we describe the evaluation of GW0742 analogs in respect to their ability to modulate transcription mediated by the Vitamin D Receptor (VDR) and the peroxisome proliferator activated receptor (PPAR)δ. The GW0742 analog bearing carboxylic ester functionality in place of the carboxylic acid was partially activating both nuclear receptors at low concentration and inhibited transcription at higher compound concentrations. The GW0742 alcohol derivative was more active than the ester in respect to VDR but less active in regard to PPARδ. Importantly, the alcohol derivative was significantly more toxic than the corresponding acid and ester.
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