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 (23):

By Effects:	Ligands (2) Agonists (6) Degraders (4) Antagonists (2) Activators (6) Modulator (1)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-131723

Pregnenolone 16α-carbonitrile	Activator	98.48%
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	99.80%
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-162704

JMV7048	Degrader	99.12%
JMV7048 is an effective PROTAC degrader targeting PXR (Pregnane X Receptor) with a DC₅₀ of 379 nM. JMV7048 induces the polyubiquitination and degradation of PXR protein by recruiting E3 CRBN ubiquitin ligase and the 26S proteasome. JMV7048 significantly enhances the sensitivity of colon cancer stem cells to chemotherapy by reducing the expression of PXR protein in these cells, thereby significantly delaying cancer recurrence in vivo. JMV7048 is composed of the PXR agonist JMV6944 (HY-162738), linker (HY-162736), and Thalidomide 5-fluoride (HY-W087383) (Red: JMV6944; Blue: Thalidomide 5-fluoride ligand; Black: linker).

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).

HY-175267

PXR Ligand 3
PXR Ligand 3 is a PXP ligand. PXR Ligand 3 can be used to synthesize PROTAC MI1013 (HY-175266).

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-W036120

Benzophenone-2	Modulator	99.66%
Benzophenone-2 (2,2',4,4'-Tetrahydroxybenzophenone) is an endocrine disruptor targeting pregnane X receptor (PXR) and estrogen receptor α (ERα). Benzophenone-2 regulates cytochrome P450 3A (CYP3A) expression by activating PXR. Benzophenone-2 is promising for research of UV filters.

HY-109568

Lynestrenol	Agonist	99.87%
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-111202

Pyributicarb	Activator	99.94%
Pyributicarb, a carbamate-type herbicide, is a potent activator of both CYP3A4 gene and human pregnane X receptor (hPXR).

HY-169280

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

HY-162738

JMV6944	Agonist
JMV6944 is a PXR agonist. JMV6944 competitively inhibits hPXR ligand-binding domain (LBD) binding to PXR with an IC₅₀ of 680nM. JMV6944 induces CYP3A4 mRNA expression in freshly isolated human primary human hepatocyte cultures. JMV6944 can be used for the synthesis of PROTAC PXR degrader JMV7048 (HY-162704).

HY-169264

SJYHJ-026	Degrader
SJYHJ-026 (compound 37) is a pregnane X receptor (PXR) PROTAC degrader with the DC₅₀ of 86.6 nM and maximal degradation of 66.4%. SJYHJ-026 shows cell cytotoxic aganist SNU-C4 HiBiT-PXR KI cells with the IC₅₀ values of 97.4 μM (24 h) and 99.5 μM (72 h) (Blue: VHL ligand HY-125845,Black: linker HY-43048；Pink: PXR inhibitor HY-169277).

HY-109568R

Lynestrenol (Standard)	Agonist
Lynestrenol (Standard) is the analytical standard of Lynestrenol. This product is intended for research and analytical applications. 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-175266

MI1013	Degrader
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-169277

PXR Ligand 1	Ligand
PXR Ligand 1 is a PXR Ligand and can be used for synthesis of SJYHJ-026 (HY-169264) PROTACs.

HY-169279

PROTAC SMARCA2/4-degrader-34	Degrader
PROTAC SMARCA2/4-degrader-34 (compound 38) is a potent is a potent SMARCA2 and SMARCA4 PROTAC degrader. PROTAC SMARCA2/4-degrader-34 shows PXR binding affinity with DC₅₀ value of 85.1 nM. PROTAC SMARCA2/4-degrader-34 decreases the protein expression of 3xFLAG-PXR. (Pink: Ligand for target protein (HY-169280); Black: Linker (HY-43048); Blue: Ligand for E3 ligase (HY-125845).

HY-169320

SJPYT-328	Agonist
SJPYT-328 is a PXR agonsit. PXR plays a major role in drug metabolism and drug-drug interactions.

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