2. Signaling Pathways
  3. Vitamin D Related/Nuclear Receptor
  4. Pregnane X Receptor (PXR)

Pregnane X Receptor (PXR)

Pregnane X Receptor

Pregnane X Receptor (PXR), a member of the nuclear receptor (NR) superfamily, is a ligand-activated transcription factor that plays a crucial role in the metabolism of xenobiotics and endobiotics in mammals. PXR was first recognized as an exogenous substance receptor regulating metabolizing enzymes and transporters and functioning in detoxification and drug metabolism in the liver. However, further research revealed that PXR acts as an equally important endogenous substance receptor in the metabolism and homeostasis of endogenous substances. PXR is highly distributed in small intestine, liver, rectum, colon and bladder, while its expression in other organs and tissues is either moderate, low or undetectable. PXR can be activated by numerous chemical compounds. Activated PXR, through direct binding to the genomic regions or indirect crosstalk with other transcriptional factors, controls various genes involved in biotransformation, transport, inflammation, oxidative stress and etc.
As a master regulator of xenobiotic response PXR adjusts the expression of many drug metabolizing enzymes (DME), such as cytochrome P450, uridine diphosphate (UDP)-glucuronosyltransferases, sulfotransferases and carboxylesterases. PXR also regulates drug-efflux pumps multi-drug resistance gene 1 (MDR1), MDR2, ATP-binding cassette transporter C 2 (ABCC) and anion-transporting polypeptide 2 (OATP). PXR is participated in tumor cell proliferation and growth, apoptosis and metastasis as well as in liver regeneration and hepatic proliferation, indicating the important role of PXR in cancer[1][2].

Pregnane X Receptor (PXR) Related Products (5):

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-175268
    PXR ligand-Linker Conjugate 1
    PXR ligand-Linker Conjugate 1 is a conjugate of PXR ligand and linker, which can be used to synthesize PROTAC MI1013 (HY-175266).
    PXR ligand-Linker Conjugate 1
  • HY-175267
    PXR Ligand 3
    PXR Ligand 3 is a PXP ligand. PXR Ligand 3 can be used to synthesize PROTAC MI1013 (HY-175266).
    PXR Ligand 3
  • HY-175266
    MI1013
    		Degrader
    MI1013 is a PROTAC PXR degrader (DC50 = 89 nM, Dmax = 82%). MI1013 degrades PXR in human hepatocellular carcinoma RG cells (HepaRG). MI1013 specifically and safely regulates CYP3A4 promoter activity through PXR degradation. MI1013 affects several key genes involved in sulfate conjugation (e.g., SULT1E1), bile acid synthesis (CYP7A1), gluconeogenesis (PCK1), ketone synthesis (HMGCS20), and hepatocyte proliferation (MKI67). (Pink: PXR ligand 3: HY-175267, Blue: Pomalidomide-propargyl ligand: HY-W410002, Pink + Black: PXR ligand-Linker Conjugate 1: HY-175268).
    MI1013
  • HY-175264
    MI891
    		Antagonist
    MI891 is a highly selective PXR antagonist (IC50 = 3.76 μM, Kd = 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.
    MI891
  • HY-174300
    Cholic acid-Glu
    		Activator
    Cholic acid-Glu is a derivative of Cholic acid (HY-N0324). The abundance of Cholic acid-Glu is increased in Crohn’s disease. Cholic acid-Glu increases PXR activation and significantly increases the expression of the downstream PXR target gene Cyp3a11 in small intestinal organoid tissue.
    Cholic acid-Glu