keyword
MENU ▼
Read by QxMD icon Read
search

PXR

keyword
https://www.readbyqxmd.com/read/28442602/molecular-basis-of-metabolism-mediated-conversion-of-pk11195-from-an-antagonist-to-an-agonist-of-the-constitutive-androstane-receptor
#1
Bryan Mackowiak, Linhao Li, Matthew A Welch, Daochuan Li, Jace W Jones, Scott Heyward, Maureen A Kane, Peter W Swaan, Hongbing Wang
The constitutive androstane receptor (CAR) plays an important role in xenobiotic metabolism, energy homeostasis, and cell proliferation. Antagonism of CAR represents a key strategy for studying its function and may have potential clinical applications. However, specific human CAR (hCAR) antagonists are limited and conflicting data on the activity of these compounds have been reported. PK11195, a typical peripheral benzodiazepine receptor ligand, has been established as a potent hCAR deactivator in immortalized cells; whether it inhibits hCAR activity under physiologically-relevant conditions remains unclear...
April 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28436464/glucose-dependent-regulation-of-pregnane-x-receptor-is-modulated-by-amp-activated-protein-kinase
#2
Peter O Oladimeji, Wenwei Lin, C Trent Brewer, Taosheng Chen
Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxification and clearance of drugs and foreign compounds from the liver. There has been mounting evidence of crosstalk between the drug metabolism pathway and the energy metabolism pathway, but little is known about this cross-regulation. To further delineate the energy metabolism and drug metabolism crosstalk in this study, we exposed HepG2 cells to varying glucose concentrations. We observed that PXR activity was induced under high-glucose conditions...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432535/exploring-the-carbamazepine-interaction-with-human-pregnane-x-receptor-and-effect-on-abcc2-using-in-vitro-and-in-silico-approach
#3
Gurpreet K Grewal, Khuraijam D Singh, Neha Kanojia, Chitra Rawat, Samiksha Kukal, Ajay Jajodia, Anshika Singhal, Richa Misra, Selvaraman Nagamani, Karthikeyan Muthusamy, Ritushree Kukreti
PURPOSE: Over expression of ATP-binding cassette transporters is considered one of the major reasons for non-responsiveness to antiepileptic drugs. Carbamazepine (CBZ), one of first line antiepileptic drug is known to influence ABCC2 expression but its exact molecular mechanism is unknown. METHODS: We investigated the effect of CBZ on expression of ABCC2 and pregnane X receptor (PXR) in HepG2 cell line and compared with hyperforin (agonist of PXR) and ketoconazole (antagonist of PXR) through realtime PCR and western blot assay...
April 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28430654/alpha-ketoglutarate-suppresses-the-nf-%C3%AE%C2%BAb-mediated-inflammatory-pathway-and-enhances-the-pxr-regulated-detoxification-pathway
#4
Liuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428138/pregnane-x-receptor-regulates-the-ahr-cyp1a1-pathway-and-protects-liver-cells-from-benzo-%C3%AE-pyrene-induced-dna-damage
#5
Hongmei Cui, Xinsheng Gu, Jingshu Chen, Ying Xie, Sui Ke, Jing Wu, Andrei Golovko, Benjamin Morpurgo, Chunhong Yan, Timothy D Phillips, Wen Xie, Jianyuan Luo, Zhijun Zhou, Yanan Tian
Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28414139/ligand-dependent-and-independent-regulation-of-human-hepatic-sphingomyelin-phosphodiesterase-acid-like-3a-expression-by-pregnane-x-receptor-and-crosstalk-with-liver-x-receptor
#6
Judith Jeske, Andreas Bitter, Wolfgang E Thasler, Thomas S Weiss, Matthias Schwab, Oliver Burk
Pregnane X receptor (PXR) mainly regulates xenobiotic metabolism and detoxification. Additionally, it exerts pleiotropic effects on liver physiology, which in large parts depend on transrepression of other liver-enriched transcription factors. Based on the hypothesis that lower expression levels of PXR may reduce the extent of this inhibition, an exploratory genome-wide transcriptomic profiling was performed using HepG2 cell clones with different expression levels of PXR. This screen and confirmatory real-time RT-PCR identified sphingomyelin phosphodiesterase acid-like (SMPDL) 3A, a novel nucleotide phosphodiesterase and phosphoramidase, as being up-regulated by PXR-deficiency...
April 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28413083/a-novel-nuclear-xenobiotic-receptors-ahr-pxr-car-mediated-mechanism-of-dehp-induced-cerebellar-toxicity-in-quails-coturnix-japonica-via-disrupting-cyp-enzyme-system-homeostasis
#7
Zheng-Hai Du, Jun Xia, Xiao-Chen Sun, Xue-Nan Li, Cong Zhang, Hua-Shan Zhao, Shi-Yong Zhu, Jin-Long Li
Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neurobehavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails...
April 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28408657/negative-regulation-of-human-pregnane-x-receptor-by-microrna-18a-5p-evidence-for-suppression-of-microrna-18a-5p-expression-by-rifampin-and-rilpivirine
#8
Devinder Sharma, Abdullah A Turkistani, Wenjun Chang, Catherine Hu, Zhaoming Xu, Thomas K H Chang
Small non-coding microRNAs act as post-transcriptional regulators of gene expression involved in diverse biological functions. Pregnane X receptor (PXR, NR1I2), which is a member of the superfamily of nuclear receptors, is a transcription factor governing the transport and biotransformation of various endobiotics and xenobiotics. In the present study, we identified a specific microRNA involved in regulating the expression and functionality of human PXR (hPXR). According to bioinformatics analysis employing three commonly used algorithms (TargetScan, miRanda, and DIANA-microT-CDS), miR-18a-5p was predicted to be the top candidate microRNA regulator of hPXR...
April 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28390928/itraconazole-cis-diastereoisomers-activate-aryl-hydrocarbon-receptor-ahr-and-pregnane-x-receptor-pxr-and-induce-cyp1a1-in-human-cell-lines-and-human-hepatocytes
#9
Martina Stepankova, Barbora Pastorkova, Petr Bachleda, Zdenek Dvorak
Triazole antimycotic itraconazole contains in its structure three chiral centres; therefore, it forms eight stereoisomers. Commercial preparations of itraconazole are a mixture of four cis-diastereoisomers. There is much evidence that efficacy, adverse effects, and toxicity of chiral drugs may be stereospecific. Therefore, we have prepared 4 pure cis-diastereoisomers of itraconazole and investigated their effects on transcriptional activities of xenoreceptors aryl hydrocarbon receptor AhR and pregnane X receptor PXR...
April 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28356150/pregnane-x-receptor-is-associated-with-unfavorable-survival-and-induces-chemotherapeutic-resistance-by-transcriptional-activating-multidrug-resistance-related-protein-3-in-colorectal-cancer
#10
Yan Dong, Zhe Wang, Gan-Feng Xie, Chong Li, Wen-Wei Zuo, Gang Meng, Cheng-Ping Xu, Jian-Jun Li
BACKGROUND: Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood. METHODS: Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays...
March 29, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28350814/compensatory-changes-in-cyp-expression-in-three-different-toxicology-mouse-models-car-null-cyp3a-null-and-cyp2b9-10-13-null-mice
#11
Ramiya Kumar, Linda C Mota, Elizabeth J Litoff, John P Rooney, W Tyler Boswell, Elliott Courter, Charles M Henderson, Juan P Hernandez, J Christopher Corton, David D Moore, William S Baldwin
Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#12
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation, and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDIs). The objective of this work is to determine if the transgenic (Tg) Cyp3a(-/-)Tg-3A4Hep/Int and Nr1i2/Nr1i3(-/-)-Cyp3a(-/-)Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims); with varying magnitudes of reported CYP3A4 clinical DDI...
April 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28335376/genetic-polymorphisms-contribute-to-the-individual-variations-of-imatinib-mesylate-plasma-levels-and-adverse-reactions-in-chinese-gist-patients
#13
Jing Liu, Zhiyu Chen, Hanmei Chen, Yingyong Hou, Weiqi Lu, Junyi He, Hanxing Tong, Yuhong Zhou, Weimin Cai
Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300-600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327790/association-of-nr1i2-gene-polymorphisms-and-time-of-progression-to-aids
#14
Rúbia Marília de Medeiros, Carolina Fialho Menti, Jéssica Louise Benelli, Maria Cristina Cotta Matte, Marineide Gonçalves de Melo, Sabrina Esteves de Matos Almeida, Marilu Fiegenbaum
BACKGROUND: The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE: To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28324649/sulfonamides-as-selective-nav1-7-inhibitors-optimizing-potency-pharmacokinetics-and-metabolic-properties-to-obtain-atropisomeric-quinolinone-am-0466-that-affords-robust-in-vivo-activity
#15
Russell F Graceffa, Alessandro A Boezio, Jessica Able, Steven Altmann, Loren M Berry, Christiane Boezio, John R Butler, Margaret Chu-Moyer, Melanie Cooke, Erin F DiMauro, Thomas A Dineen, Elma Feric Bojic, Robert S Foti, Robert T Fremeau, Angel Guzman-Perez, Hua Gao, Hakan Gunaydin, Hongbing Huang, Liyue Huang, Christopher Ilch, Michael Jarosh, Thomas Kornecook, Charles R Kreiman, Daniel S La, Joseph Ligutti, Benjamin C Milgram, Min-Hwa Jasmine Lin, Isaac E Marx, Hanh N Nguyen, Emily A Peterson, Gwen Rescourio, John Roberts, Laurie Schenkel, Roman Shimanovich, Brian A Sparling, John Stellwagen, Kristin Taborn, Karina R Vaida, Jean Wang, John Yeoman, Violeta Yu, Dawn Zhu, Bryan D Moyer, Matthew M Weiss
Because of its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a series of atropisomeric quinolinone sulfonamide inhibitors [ Bicyclic sulfonamide compounds as sodium channel inhibitors and their preparation . WO 2014201206, 2014 ] of NaV1...
April 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28315689/in-silico-prediction-of-hpxr-activators-using-structure-based-pharmacophore-modeling
#16
Nao Torimoto-Katori, Ruili Huang, Harutoshi Kato, Rikiya Ohashi, Menghang Xia
The activation of pregnane X receptor (PXR), a member of the nuclear receptor superfamily, can mediate potential drug-drug interactions by regulating the expression of several drug- mediated enzymes and transporters, resulting in reduced therapeutic efficacy or increased toxicity by producing reactive metabolites. Therefore, in the early stage of drug development, it is important to predict these risks using an in silico approach. We constructed a human PXR (hPXR) pharmacophore model based on known structural information of compounds that activate PXR...
March 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#17
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28303499/pregnane-x-receptor-not-nuclear-factor-kappa-b-up-regulates-p-glycoprotein-expression-in-the-brain-of-chronic-epileptic-rats-induced-by-kainic-acid
#18
Nian Yu, Yan-Fang Zhang, Kang Zhang, Yong-Fei Cheng, Hai-Yan Ma, Qing Di
Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28289823/human-pregnane-x-receptor-is-activated-by-dibenzazepine-carbamate-based-inhibitors-of-constitutive-androstane-receptor
#19
Judith Jeske, Björn Windshügel, Wolfgang E Thasler, Matthias Schwab, Oliver Burk
Unintentional activation of xenosensing nuclear receptors pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR) by clinical drug use is known to produce severe side effects in patients, which may be overcome by co-administering antagonists. However, especially antagonizing CAR is hampered by the lack of specific inhibitors, which do not activate PXR. Recently, compounds based on a dibenzazepine carbamate scaffold were identified as potent CAR inhibitors. However, their potential to activate PXR was not thoroughly investigated, even if the lead compound was named "CAR inhibitor not PXR activator 1" (CINPA1)...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28288941/differential-activation-of-pregnane-x-receptor-by-carnosic-acid-carnosol-ursolic-acid-and-rosmarinic-acid
#20
Chun Ling Seow, Aik Jiang Lau
Pregnane X receptor (PXR) regulates the expression of many genes, including those involved in drug metabolism and transport, and has been linked to various diseases, including inflammatory bowel disease. In the present study, we determined whether carnosic acid and other chemicals in rosemary extract (carnosol, ursolic acid, and rosmarinic acid) are PXR activators. As assessed in dual-luciferase reporter gene assays, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, activated human PXR (hPXR) and mouse PXR (mPXR), whereas carnosol and ursolic acid, but not carnosic acid or rosmarinic acid, activated rat PXR (rPXR)...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
keyword
keyword
107627
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"