Selective targeting of PPARγ by the natural product chelerythrine with a unique binding mode and improved antidiabetic potency

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Selective targeting of PPARγ by the natural product chelerythrine with a unique binding mode and improved antidiabetic potency

Type 2 diabetes mellitus (T2DM) is a pervasive metabolic syndrome that is characterized by insulin resistance, hyperglycemia and dyslipidemia. As full agonists of PPARγ, thiazolidinedione (TZD) drugs elicit antidiabetic effects by targeting PPARγ but is accompanied by weight gain, fluid retention and cardiovascular risk associated with their transcriptional agonism potency. We here identify a n...

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Identification of a novel selective PPARγ ligand with a unique binding mode and improved therapeutic profile in vitro

Thiazolidinediones (TZD) function as potent anti-diabetic drugs through their direct action on the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), but their therapeutic benefits are compromised by severe side effects. To address this concern, here we developed a potent "hit" compound, VSP-51, which is a novel selective PPARγ-modulating ligand with improved therapeutic pro...

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ژورنال

عنوان ژورنال: Scientific Reports

سال: 2015

ISSN: 2045-2322

DOI: 10.1038/srep12222