PXR _ NR1I2
- Known as:
- PXR _ NR1I2
- Catalog number:
- Y214223
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- PXR _ NR1I2
Related genes to: PXR _ NR1I2
- Gene:
- NR1I2 NIH gene
- Name:
- nuclear receptor subfamily 1 group I member 2
- Previous symbol:
- -
- Synonyms:
- ONR1, PXR, BXR, SXR, PAR2
- Chromosome:
- 3q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-23
- Date modifiied:
- 2016-10-05
Related products to: PXR _ NR1I2
Related articles to: PXR _ NR1I2
- Yes-associated protein (YAP) is a critical factor of the Hippo pathway, which plays a key role in regulating organ size. Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and peroxisome proliferator-activated receptor α (PPARα) are key members of the nuclear receptor superfamily, known for mediating diverse physiological and biological processes. Previous studies have demonstrated that activation of PXR, CAR, or PPARα promotes hepatomegaly and liver regeneration via YAP signaling. YAP has been reported to undergo phase separation under hyperosmotic stress, leading to enhanced expression of downstream target genes. However, it remains unknown whether PXR, CAR, or PPARα activation affects the phase separation of YAP. Therefore, this study aimed to investigate the potential effects of PXR, CAR, and PPARα activation on YAP phase separation using live-cell imaging and fluorescence recovery after photobleaching assay. The results suggested that YAP underwent phase separation under hyperosmotic stress in cells, which was associated with increased mRNA and protein expression of YAP target genes. Further live-cell imaging revealed that neither PXR, CAR, nor PPARα activation induced YAP phase separation under physiological conditions or affected its phase separation under hyperosmotic stress. In conclusion, these findings demonstrate that activation of PXR, CAR, or PPARα does not induce YAP phase separation under physiological conditions or under hyperosmotic stress. SIGNIFICANCE STATEMENT: Yes-associated protein (YAP) plays a crucial role in regulating organ size. Activation of pregnane X receptor, constitutive androstane receptor, or peroxisome proliferator-activated receptor α promotes hepatomegaly and liver regeneration via YAP signaling. This study demonstrates that activation of pregnane X receptor, constitutive androstane receptor, and peroxisome proliferator-activated receptor α does not induce YAP phase separation under either physiological conditions or hyperosmotic stress, which contributes to further understanding of the regulatory mechanisms involving pregnane X receptor, constitutive androstane receptor, peroxisome proliferator-activated receptor α, and YAP, providing new insights into their physiological functions. - Source: PubMed
Publication date: 2026/03/16
Pengfei Zhao Fan ShichengZhou YanyingTian JianingHuang MinLai YongZuo ZhongBi HuichangGao Yue - Control of schistosomiasis, a neglected tropical disease caused by infection with ., remains reliant on a single chemotherapy, praziquantel (PZQ). This strategy presents a risk to global health should PZQ-resistant schistosomes establish in endemic areas and justifies the search for new drugs. However, species-specific metabolic differences between humans and preclinical models hinder the optimization of next-generation anti-schistosomal therapeutics. Here, to bypass these species-specific limitations, we exploited a humanized mouse model, 8HUM, engineered to express the principal human Phase I cytochrome P450 enzymes (CYP1A1/2, CYP2C9, CYP2D6, CYP3A4/7) as well as the transcription factors constitutive androstane receptor and pregnane X receptor in place of 35 murine orthologs. We characterized development, immunopathology, hepatic transcriptomic responses, intestinal microbiome changes, and PZQ metabolism as well as PZQ efficacy in 8HUM vs. wild-type (WT) mice. 8HUM mice supported normal maturation, infection-associated microbiome dysbiosis, Th2-dominant immune responses, and characteristic hepatic pathology. PZQ intrinsic clearance in 8HUM hepatic microsomes mirrored human levels and was >10-fold lower than that found for WT microsomes. Oral dosing revealed human-like PZQ exposures of ()-PZQ and 4OH-PZQ in 8HUM mice at 25 mg/kg bodyweight and >90% reductions in worm burdens at 100 mg/kg bodyweight (equivalent to that seen in WT mice administered PZQ at 400 mg/kg bodyweight). Our results revealed that 8HUM mice recapitulate key features of murine schistosomiasis while exhibiting human-relevant drug metabolism. These findings establish 8HUM as a refined translational platform for anti-schistosomal drug development, improving predictive accuracy and accelerating therapeutic discovery. - Source: PubMed
Publication date: 2026/04/10
Davey Sarah DForde-Thomas Josephine EHulme Benjamin JLees KristinCostain Alice HEvans MaryRinaldi GabrielFrame LauraStojanovski LasteSimeons Frederick R CTavendale AmyMacLeod A KennethPichon RemiLee Yi-HsuanPolak OktawiaChalmers Iain WDankwa BismarkOdhiambo Brenda KisiaGuimaraes Victor HugoHegarty MatthewSwain Martin TAubrey WayneCaldwell NicolaMacDonald Andrew SGilbert Ian HBaragaña BeatrizRead Kevin DHoffmann Karl F - Atorvastatin (ATO) is a widely prescribed lipid-lowering drug, but its use can be limited by hepatotoxicity, potentially linked to metabolism-related mechanisms. The cellular pathways connecting ATO metabolism to oxidative imbalance and apoptotic alterations remain incompletely defined. This study examined the roles of oxidative stress, mitochondrial-associated apoptosis, and the pregnane X receptor (PXR)-CYP3A4 axis in ATO-induced hepatic changes, and evaluated whether coenzyme Q10 (CoQ10) could modulate these effects depending on administration timing. - Source: PubMed
Publication date: 2026/04/09
Abdel-Rasol Mohammed AAnwar Mohamed STaha Hoda AEl-Sayed Wael MAbdelRaouf Kholoud - Understanding the molecular determinants of interindividual drug response variability remains a major challenge in pharmacogenomics. Very Important Pharmacogenes (VIPs), as defined by PharmGKB, represent genes with well-established roles in drug metabolism and efficacy. However, their activity occurs within complex molecular networks that extend beyond direct pharmacogenetic associations. We constructed a VIP-centered subnetwork and applied network topology analyses, including shortest path, signal propagation, and degree centrality, to identify key nodes mediating VIP interactions. Functional enrichment, transcription factor (TF) association, and drug-gene interaction analyses were subsequently performed to characterize the biological and pharmacological context of these networks. Our results revealed a dense VIP interactome enriched in metabolic, endocrine, and signaling pathways. Notably, we identified a subset of highly connected non-VIP genes that frequently bridge canonical VIPs, termed shadow VIPs. These genes, often encoding transcriptional regulators, such as , , and , and more frequent in the shortest paths connecting VIPs, such as POR, APP, and GIPC1, exhibited strong associations with approved drugs, particularly hormone-related and antineoplastic agents. This suggests that shadow VIPs may act as indirect regulators of pharmacogenomic phenotypes by influencing the expression or activity of canonical VIPs. Additionally, the analysis revealed that shadow VIPs, on average, exhibit lower RVIS values than VIPs, indicating a higher intolerance to functional mutations. This suggests that shadow VIPs are under stronger selective selection, underscoring their essential biological roles. Together, these findings expand the current pharmacogenomic framework, demonstrating that drug response mechanisms emerge from a wider network of regulatory and functional interactions. Introducing the concept of shadow VIPs highlights new molecular candidates for pharmacogenetic exploration and emphasizes the value of network-based approaches in advancing precision medicine. - Source: PubMed
Publication date: 2026/03/19
de Melo Nicolly ClementeAccioli Guilherme SilvaSánchez-Luquez KarenGomes Mateus Freitas de FariasFelicio Aline Cristinade Carvalho Lucas Miguel - Mycotoxins are prominent environmental pollutants that pose serious health risks. Deoxynivalenol (DON), a trichothecene mycotoxin, is a widespread food contaminant known to cause metabolic and hepatotoxic effects in humans and animals. Although DON-induced inflammatory responses and ribotoxic stress are well characterized, its impact on xenobiotic metabolism and disposition machinery remains unclear. The pregnane X receptor (PXR) is a ligand-activated nuclear receptor that functions as the "master regulator" of detoxification and disposition machinery, including several enzymes and drug transporters. In this study, we investigated the molecular mechanism of DON-induced impairment of PXR. It is revealed that DON selectively induces nuclear translocation of PXR and its heterodimeric partner, retinoid X receptor, implying intermolecular interactions. The DON-PXR interaction appears to impair PXR transcription function, reflected in reduced transcriptional induction of key xenobiotic-metabolizing enzymes. Surprisingly, DON-induced cellular toxicity appeared to occur through generation of alternate translational isoforms of PXR. Additionally, DON disrupted receptor-chromatin interactions exhibited by PXR during mitosis. This apparently led to loss of regulatory control of PXR over the xenobiotic metabolism and disposition, thereby increasing the retention of toxicants. The findings provide the first evidence that DON acts via functional impairment of PXR, revealing a novel mechanism by which environmental mycotoxins can perturb nuclear receptor function and cellular homeostasis. SIGNIFICANT STATEMENT: The study reveals a previously unrecognized molecular mechanism by which deoxynivalenol impairs hepatic detoxification by disrupting pregnane X receptor function and chromatin interactions. Deoxynivalenol interferes as a pregnane X receptor antagonist by reducing transcription function and aberrant isoform generation, highlighting a novel pathway by which mycotoxins may influence nuclear receptor-mediated hepatic homeostasis. - Source: PubMed
Publication date: 2026/03/13
Rizvi SheebaShandilya PriyankaThakur KeshavKumari NehaTyagi Rakesh K