Pregnane X Receptor (PXR) Antagonist

SJPYT-310 is a selective PXR antagonist. SJPYT-310 shows no significant cytotoxicity.

MI-883 is orally active constitutive androstane receptor (CAR) (EC₅₀ of 73 nM) agonist and pregnane X Receptor (PXR) (IC₅₀ of 100 nM) antagonist. MI-883 binds to CAR and PXR ligand-binding domains, promotes CAR LBD assembly, activates CAR3 variant, stimulates CAR cytoplasmic-nuclear translocation, upregulates CAR target genes, recruits coactivators NCOA1, NCOA2, NCOA3, inhibits basal and agonist-induced PXR activation, downregulates PXR target genes, disrupts PXR-NCOR2 interaction, blocks agonist-mediated PXR-NCOA1 recruitment. MI-883 reduces plasma total cholesterol, LDL cholesterol, and hepatic free cholesterol levels, increases fecal bile acid excretion, regulates genes involved in xenobiotic metabolism, cholesterol homeostasis, and bile acid homeostasis. MI-883 exhibits metabolic stability, liver-predominant distribution, a safety profile with no observed toxicity, and does not stimulate human hepatocyte hypertrophy or hyperplasia. MI-883 can be used for the research of diet-induced hypercholesterolemia.

MI891 is a highly selective PXR antagonist (IC₅₀ = 3.76 μM, K_d = 1.7 μM) and inverse agonist (IC₅₀ = 6.1 μM). MI891 selectively disrupts the interaction between PXR and its coactivator SRC1. MI891 effectively inhibits Rifampicin (HY-B0272)-induced PXR activation. MI891 is useful for the study of metabolic diseases and other diseases.