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The hypolipidemic effect of MI-883, the combined CAR agonist/ PXR antagonist, in diet-induced hypercholesterolemia model
Nature Communications 16: 1418 (2025)
Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related nuclear receptors with overlapping regulatory functions in xenobiotic clearance but distinct roles in endobiotic metabolism. Car activation has been demonstrated to ameliorate hypercholesterolemia by regulating cholesterol metabolism and bile acid elimination, whereas PXR activation is associated with hypercholesterolemia and liver steatosis. Here we show a human CAR agonist/PXR antagonist, MI-883, which effectively regulates genes related to xenobiotic metabolism and cholesterol/bile acid homeostasis by leveraging CAR and PXR interactions in gene regulation. Through comprehensive analyses utilizing lipidomics, bile acid metabolomics, and transcriptomics in humanized PXR-CAR-CYP3A4/3A7 mice fed high-fat and high-cholesterol diets, we demonstrate that MI-883 significantly reduces plasma cholesterol levels and enhances fecal bile acid excretion. This work paves the way for the development of ligands…
CDK2-based CDK7 mimic as a tool for structural analysis: Biochemical validation and crystal structure with SY5609
International Journal of Biological Macromolecules 294: 139117 (2025)
Simultaneous treatment with palm-LEAP2(1–14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1–14)
Molecular and Cellular Endocrinology 597: 112442 (2025)
Chiroptical spectroscopy complemented by quantum chemical calculations accurately predicts the absolute configuration of P-chirogenic compounds
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 330: 125674 (2025)