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].

References:

[1]. Skandalaki A, et, al. Pregnane X Receptor (PXR) Polymorphisms and Cancer Treatment. Biomolecules. 2021 Aug 2;11(8):1142. [Content Brief]

[2]. Lv Y, et, al. The role of pregnane X receptor (PXR) in substance metabolism. Front Endocrinol (Lausanne). 2022 Aug 16:13:959902. [Content Brief]

Pregnane X Receptor (PXR) Related Products (38):

By Effects:	Inhibitor (1) Agonists (10) Degraders (3) Ligands (4) Antagonists (3) Activators (12) Chemicals (2)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-131723

Pregnenolone 16α-carbonitrile	Activator	98.42%
Pregnenolone 16α-carbonitrile is an orally active prototypical and effective rodent-PXR activator. Pregnenolone 16α-carbonitrile, a synthetic steroid, induces cytochrome P450 3A expression. Pregnenolone 16α-carbonitrile exhibits increased resistance to subsequent stressful insults.

HY-100793

SR12813	Agonist	99.84%
SR12813 (GW 485801) is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, with an IC₅₀ value of 0.85 μM. SR12813 is also an efficient agonist of human pregnane X receptor (hPXR). SR12813 can strongly bind to hPXR but not to mouse PXR (mPXR).

HY-119459

Fluopyram	Activator	99.76%
Fluopyram is an orally active succinate dehydrogenase inhibitor, antifungal and nematicide. Fluopyram inhibits succinate dehydrogenase activity, activates CAR/PXR nuclear receptors, and increases caspase-3, TNF-α and NF-κB. Fluopyram inhibits the growth of F. virguliforme, Botrytis cinerea and Alternaria solani with EC₅₀ values of 3.35, 5.389 and 0.244 µg/mL, respectively. Fluopyram induces liver and thyroid tumor formation. Fluopyram is nephrotoxic and embryotoxic.

HY-B1134

Imazalil	Activator	99.54%
Imazalil (Enilconazole) is a fungicide. Imazalil has oral activity and strongly activates mPXR but not mCAR in mouse liver. Imazalil is commonly used to protect various agricultural crops against fungal attack. Imazalil induces developmental abnormalities, gut microbiota dysbiosis, and hepatic metabolism disorder.

HY-173072

SJPYT-310	Antagonist	99.9%
SJPYT-310 is a selective PXR antagonist. SJPYT-310 shows no significant cytotoxicity.

HY-N19818

Glycybridin C	Ligand
Glycybridin C is a Protein tyrosine phosphatase 1B (PTP1B) inhibitor and pregnane X receptor (PXR) ligand. Glycybridin C inhibits insulin and leptin signaling pathway negative regulation, LPS (HY-D1056)-induced NF-κB transcriptional activity. Glycybridin C forms hydrophobic and π-π stacking interactions with Met243, Phe288, Tyr306, and His407 residues of PXR. Glycybridin C can be used for the research of hepatocellular carcinoma, colorectal adenocarcinoma, breast carcinoma.

HY-180918

ERG-IN-4	Activator
ERG-IN-4 (Compound 12) is an orally active, selective ERG inhibitor with an IC₅₀ of 5.2 μM for hERG. ERG-IN-4 activates PXR. ERG-IN-4 exhibits anticancer activity against MTAP-deleted non-small cell lung cancer.

HY-122163

MK-3901	Activator
MK-3901 is a selective P2X3 receptor antagonist with an IC₅₀ of 24 nM. MK-3901 inhibits UGT1A1 (with an IC₅₀ of 1 μM) and CYP2C9 (with an IC₅₀ of 5.7 μM). MK-3901 activates PXR. MK-3901 induces hyperbilirubinemia. MK-3901 can be used for the research of inflammatory pain.

HY-W036120

Benzophenone-2		99.66%
Benzophenone-2 (2,2',4,4'-Tetrahydroxybenzophenone) is an organic ultraviolet absorber that is widely used in personal care products and industrial products such as plastics and coatings. Benzophenone-2 is an endocrine disruptor that can interfere with estrogen receptors (ERα receptor) and pregnane X receptor (PXR receptor) activity, leading to reproductive toxicity, immune disorders, and metabolic abnormalities. Benzophenone-2 can inhibit the activity of α-glucosidase (IC₅₀ = 49.72 μM), and can be used for research on diabetes.

HY-150616

SJPYT-195	Inhibitor	98.07%
SJPYT-195 is a cytotoxic GSPT1 degrader and can be used for PROTAC synthesis.

HY-109568

Lynestrenol	Agonist	99.92%
Lynestrenol is a pregnane X receptor (PXR) agonist with the EC₅₀s of 41 and 0.23 μM for hPXR and zfPXR, respectively. Lynestrenol, a synthetic progesteronelike agent possess immunostimulatory properties.

HY-N4246

Bacopaside I	Chemical	99.20%
Bacopaside I is an orally active aquaporin AQP1 inhibitor and PKC modulator with neuroprotective and anticancer activities. Bacopaside I specifically blocks the water channel and cGMP-gated ion channel activities of AQP1 without affecting AQP4, thereby inhibiting the migration of colon cancer cells expressing AQP1. Bacopaside I activates the Akt pathway by interacting with PI3K, specifically inhibits MAO-A, effectively alleviates neuron necrosis and apoptosis induced by oxygen-glucose deprivation, reduces oxidative stress, and regulates the surface expression of neuroreceptors. When combined with Bacopaside II (HY-N6016), Bacopaside I significantly reduces the viability, proliferation and invasion ability of breast cancer cells, and binds to the pregnane X receptor (PXR). Bacopaside I is applicable to the research of colon cancer, breast cancer, vascular dementia, cerebral ischemia and other related diseases.

HY-W587839

4,8-Dioxa-3H-perfluorononanoic acid	Agonist
4,8-Dioxa-3H-perfluorononanoic acid is an ether-substituted polyfluoroalkyl compound and also a ligand of human pregnane X receptor (hPXR), which binds to the ligand-binding domain of hPXR. 4,8-Dioxa-3H-perfluorononanoic acid targets Arg-410, Lys-210, Lys-226, Met-323 and His-327 residues. Its binding process relies on long-range electrostatic interactions, and no significant hydrogen bonds form with hPXR residues. 4,8-Dioxa-3H-perfluorononanoic acid is used as a substitute for PFOA in Germany. 4,8-Dioxa-3H-perfluorononanoic acid is detectable in environmental matrices such as river water near fluoride production plants, accumulates in organisms including grass, deer liver and locusts, and is present in plasma samples of populations in southern Germany.

HY-W023836

4-Chloro-2-(trifluoroacetyl)aniline	Ligand
4-Chloro-2-(trifluoroacetyl)aniline (Compound 10), an analog of Efavirenz (HY-10572), is a Pregnane X receptor (PXR) ligand. 4-Chloro-2-(trifluoroacetyl)aniline has no PXR activation activity without induction of Cyp3a11 mRNA expression.

HY-173033

MI-883	Antagonist
MI-883 is the orally active agonist for Constitutive Androstane Receptor (CAR, EC₅₀=73 nM) and the antagonist for Pregnane X Receptor (PXR, IC₅₀=0.1 μM). MI-883 stimulates CAR LBD assembly (EC₅₀=0.38 µM) and CAR3 variant activation (EC₅₀=0.074 µM), induces CYP2B6 mRNA expression in HepaRG and primary human hepatocytes. MI-883 inhibits basal PXR activity IC₅₀=2.03 µM) in transiently transfected HepG2 cells, blocks CYP3A4 mRNA expression in HepG2. MI-883 regulates cholesterol metabolism and bile acid excretion, improves hypercholesterolemia in mouse models.

HY-175266

MI1013	Degrader	99.10%
MI1013 is a PROTAC PXR degrader (DC₅₀ = 89 nM, D_max = 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).

HY-175264

MI891	Antagonist
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.

HY-N6023

Thermopsoside	Activator	98.0%
Thermopsoside is a CYP450 isoenzyme inhibitor and PXR activator. Thermopsoside inhibits CYP3A4, CYP2C19, CYP2D6 and CYP2C9 with IC₅₀ values of 6.0 μM, 9.5 μM, 12.0 μM and 32.0 μM, respectively.

HY-N9454

Garcinoic acid	Agonist
Garcinoic acid is an orally active anti-inflammatory agent that crosses the blood-brain barrier. Garcinoic acid also enhances efferocytosis and enzyme/receptor regulation, and selectively inhibits human COX-2, porcine α-amylase, Saccharomyces cerevisiae α-glucosidase and human DNA polymerase β (IC₅₀=11 μM), as well as activates human PXR. Garcinoic acid enhances macrophage efferocytosis via receptors such as MerTK and LRP-1, and promotes the production of pro-resolving lipid mediators. Garcinoic acid inhibits NF-κB activation and pro-inflammatory cytokine secretion, interferes with Aβ aggregation, downregulates NLRP3 inflammasome activity, and binds to targets including CD44 and EGFR to inhibit leukemia cell proliferation. The pharmacological activities of Garcinoic acid, such as antioxidant, anti-inflammatory and lipid metabolism-regulating effects, are widely used in studies related to various diseases including atherosclerosis, Alzheimer's disease, type 2 diabetes, inflammatory bowel disease and viral pneumonia.

HY-169280

PXR Ligand 2	Ligand
PXR Ligand 2 (Compound 55) is the target protein ligand for PROTAC SMARCA2/4-degrader-34 (HY-169279).

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