当前位置： SCI文献检索 > Nature Communications期刊下所有文献 > SPA70 is a potent antagonist of human pregnane X receptor.

SPA70 is a potent antagonist of human pregnane X receptor.

Abstract：

:Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report that SPA70 is a potent and selective hPXR antagonist. SPA70 inhibits hPXR in human hepatocytes and humanized mouse models and enhances the chemosensitivity of cancer cells, consistent with the role of hPXR in drug resistance. Unexpectedly, SJB7, a close analog of SPA70, is an hPXR agonist. X-ray crystallography reveals that SJB7 resides in the ligand-binding domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding. Differential hydrogen/deuterium exchange analysis demonstrates that SPA70 and SJB7 interact with the hPXR LBD. Docking studies suggest that the lack of the para-methoxy group in SPA70 compromises its interaction with the AF-2, thus explaining its antagonism. SPA70 is an hPXR antagonist and promising therapeutic tool.The xenobiotic-activated human pregnane X receptor (hPXR) regulates drug metabolism. Here the authors develop hPXR modulators, which are of potential therapeutic interest and functionally and structurally characterize the antagonist SPA70 and the structurally related agonist SJB7.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lin W,Wang YM,Chai SC,Lv L,Zheng J,Wu J,Zhang Q,Wang YD,Griffin PR,Chen T

doi

10.1038/s41467-017-00780-5

subject

Has Abstract

pub_date

2017-09-29 00:00:00

pages

741

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00780-5

journal_volume

8

pub_type

杂志文章

相关文献

Nature Communications文献大全
  • Elastic anisotropy of experimental analogues of perovskite and post-perovskite help to interpret D'' diversity.

    abstract：:Recent studies show that the D'' layer, just above the Earth's core-mantle boundary, is composed of MgSiO3 post-perovskite and has significant lateral inhomogeneity. Here we consider the D'' diversity as related to the single-crystal elasticity of the post-perovskite phase. We measure the single-crystal elasticity of ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms4453

    authors： Yoneda A,Fukui H,Xu F,Nakatsuka A,Yoshiasa A,Seto Y,Ono K,Tsutsui S,Uchiyama H,Baron AQ

    更新日期：2014-03-27 00:00:00

  • Control of transmembrane charge transfer in cytochrome c oxidase by the membrane potential.

    abstract：:The respiratory chain in mitochondria is composed of membrane-bound proteins that couple electron transfer to proton translocation across the inner membrane. These charge-transfer reactions are regulated by the proton electrochemical gradient that is generated and maintained by the transmembrane charge transfer. Here,...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-05615-5

    authors： Björck ML,Brzezinski P

    更新日期：2018-08-09 00:00:00

  • Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome.

    abstract：:The transcriptional regulatory network (TRN) of Bacillus subtilis coordinates cellular functions of fundamental interest, including metabolism, biofilm formation, and sporulation. Here, we use unsupervised machine learning to modularize the transcriptome and quantitatively describe regulatory activity under diverse co...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-20153-9

    authors： Rychel K,Sastry AV,Palsson BO

    更新日期：2020-12-11 00:00:00

  • Rebalancing of internally generated carriers for mid-infrared interband cascade lasers with very low power consumption.

    abstract：:The interband cascade laser differs from any other class of semiconductor laser, conventional or cascaded, in that most of the carriers producing population inversion are generated internally, at semimetallic interfaces within each stage of the active region. Here we present simulations demonstrating that all previous...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms1595

    authors： Vurgaftman I,Bewley WW,Canedy CL,Kim CS,Kim M,Merritt CD,Abell J,Lindle JR,Meyer JR

    更新日期：2011-12-13 00:00:00

  • Dynamic evolution and reversibility of single-atom Ni(II) active site in 1T-MoS2 electrocatalysts for hydrogen evolution.

    abstract：:1T-MoS2 and single-atom modified analogues represent a highly promising class of low-cost catalysts for hydrogen evolution reaction (HER). However, the role of single atoms, either as active species or promoters, remains vague despite its essentiality toward more efficient HER. In this work, we report the unambiguous ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-17904-z

    authors： Pattengale B,Huang Y,Yan X,Yang S,Younan S,Hu W,Li Z,Lee S,Pan X,Gu J,Huang J

    更新日期：2020-08-17 00:00:00

  • Author Correction: EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature communications

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41467-020-17430-y

    authors： Jiang L,Shen Y,Guo D,Yang D,Liu J,Fei X,Yang Y,Zhang B,Lin Z,Yang F,Wang X,Wang K,Wang J,Cai Z

    更新日期：2020-07-16 00:00:00

  • Manipulating dehydrogenation kinetics through dual-doping Co3N electrode enables highly efficient hydrazine oxidation assisting self-powered H2 production.

    abstract：:Replacing sluggish oxygen evolution reaction (OER) with hydrazine oxidation reaction (HzOR) to produce hydrogen has been considered as a more energy-efficient strategy than water splitting. However, the relatively high cell voltage in two-electrode system and the required external electric power hinder its scalable ap...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-15563-8

    authors： Liu Y,Zhang J,Li Y,Qian Q,Li Z,Zhu Y,Zhang G

    更新日期：2020-04-15 00:00:00

  • EPR-aided approach for solution structure determination of large RNAs or protein-RNA complexes.

    abstract：:High-resolution structural information on RNA and its functionally important complexes with proteins is dramatically underrepresented compared with proteins but is urgently needed for understanding cellular processes at the molecular and atomic level. Here we present an EPR-based protocol to help solving large RNA and...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms4669

    authors： Duss O,Yulikov M,Jeschke G,Allain FH

    更新日期：2014-05-14 00:00:00

  • Magnetically driven active topography for long-term biofilm control.

    abstract：:Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics. To address this unmet challenge, we engineer tunable active surface topographies with micron-sized pillars that can beat at a programmable frequency and force level in an electroma...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-16055-5

    authors： Gu H,Lee SW,Carnicelli J,Zhang T,Ren D

    更新日期：2020-05-05 00:00:00

  • Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter.

    abstract：:Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing rel...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-12264-9

    authors： Condon MD,Platt NJ,Zhang YF,Roberts BM,Clements MA,Vietti-Michelina S,Tseu MY,Brimblecombe KR,Threlfell S,Mann EO,Cragg SJ

    更新日期：2019-09-19 00:00:00

  • Supramolecular amplification of amyloid self-assembly by iodination.

    abstract：:Amyloid supramolecular assemblies have found widespread exploitation as ordered nanomaterials in a range of applications from materials science to biotechnology. New strategies are, however, required for understanding and promoting mature fibril formation from simple monomer motifs through easy and scalable processes....

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms8574

    authors： Bertolani A,Pirrie L,Stefan L,Houbenov N,Haataja JS,Catalano L,Terraneo G,Giancane G,Valli L,Milani R,Ikkala O,Resnati G,Metrangolo P

    更新日期：2015-06-30 00:00:00

  • Amplification of future energy demand growth due to climate change.

    abstract：:Future energy demand is likely to increase due to climate change, but the magnitude depends on many interacting sources of uncertainty. We combine econometrically estimated responses of energy use to income, hot and cold days with future projections of spatial population and national income under five socioeconomic sc...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-10399-3

    authors： van Ruijven BJ,De Cian E,Sue Wing I

    更新日期：2019-06-24 00:00:00

  • Impurity-band transport in organic spin valves.

    abstract：:The central phenomenon in the field of organic spintronics is the large magnetoresistance in thick organic spin valves. A prerequisite for understanding the magnetoresistance is a reliable description of the device resistance, or the I-V characteristics. Here I show that the observed I-V characteristics in the organic...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5842

    authors： Yu ZG

    更新日期：2014-09-09 00:00:00

  • TAF1 plays a critical role in AML1-ETO driven leukemogenesis.

    abstract：:AML1-ETO (AE) is a fusion transcription factor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that TATA-Box Binding Protein Associated Factor 1 (TAF1) associates with K43 acetylated AE and this association plays a pivotal role in the proliferation of AE-e...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-12735-z

    authors： Xu Y,Man N,Karl D,Martinez C,Liu F,Sun J,Martinez CJ,Martin GM,Beckedorff F,Lai F,Yue J,Roisman A,Greenblatt S,Duffort S,Wang L,Sun X,Figueroa M,Shiekhattar R,Nimer S

    更新日期：2019-10-29 00:00:00

  • A shape-shifting redox foldase contributes to Proteus mirabilis copper resistance.

    abstract：:Copper resistance is a key virulence trait of the uropathogen Proteus mirabilis. Here we show that P. mirabilis ScsC (PmScsC) contributes to this defence mechanism by enabling swarming in the presence of copper. We also demonstrate that PmScsC is a thioredoxin-like disulfide isomerase but, unlike other characterized p...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms16065

    authors： Furlong EJ,Lo AW,Kurth F,Premkumar L,Totsika M,Achard MES,Halili MA,Heras B,Whitten AE,Choudhury HG,Schembri MA,Martin JL

    更新日期：2017-07-19 00:00:00

  • Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling.

    abstract：:The mammary epithelium comprises two primary cellular lineages, but the degree of heterogeneity within these compartments and their lineage relationships during development remain an open question. Here we report single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-017-01560-x

    authors： Pal B,Chen Y,Vaillant F,Jamieson P,Gordon L,Rios AC,Wilcox S,Fu N,Liu KH,Jackling FC,Davis MJ,Lindeman GJ,Smyth GK,Visvader JE

    更新日期：2017-11-20 00:00:00

  • Nuclear Nestin deficiency drives tumor senescence via lamin A/C-dependent nuclear deformation.

    abstract：:Emerging evidence has revealed that Nestin not only serves as a biomarker for multipotent stem cells, but also regulates cell proliferation and invasion in various tumors. However, the mechanistic contributions of Nestin to cancer pathogenesis are still unknown. In the present study, previously thought to reside exclu...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-05808-y

    authors： Zhang Y,Wang J,Huang W,Cai J,Ba J,Wang Y,Ke Q,Huang Y,Liu X,Qiu Y,Lu Q,Sui X,Shi Y,Wang T,Shen H,Guan Y,Zhou Y,Chen Y,Wang M,Xiang AP

    更新日期：2018-09-06 00:00:00

  • Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties.

    abstract：:Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-defici...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-14338-5

    authors： Terashima Y,Toda E,Itakura M,Otsuji M,Yoshinaga S,Okumura K,Shand FHW,Komohara Y,Takeda M,Kokubo K,Chen MC,Yokoi S,Rokutan H,Kofuku Y,Ohnishi K,Ohira M,Iizasa T,Nakano H,Okabe T,Kojima H,Shimizu A,Kanegasaki S,

    更新日期：2020-01-30 00:00:00

  • Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders.

    abstract：:Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-12869-0

    authors： Oetjens MT,Kelly MA,Sturm AC,Martin CL,Ledbetter DH

    更新日期：2019-10-25 00:00:00

  • Neutralization mechanism of a highly potent antibody against Zika virus.

    abstract：:The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the ant...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms13679

    authors： Zhang S,Kostyuchenko VA,Ng TS,Lim XN,Ooi JSG,Lambert S,Tan TY,Widman DG,Shi J,Baric RS,Lok SM

    更新日期：2016-11-24 00:00:00

  • Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans.

    abstract：:Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences (rDNA) encoding ribosomal RNAs (rRNAs) are tandemly repeated and give origin to the nucleolus. Here we develop a computational method for estimating rDNA dosage (copy number) and mitochondrial DNA abundance using w...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5850

    authors： Gibbons JG,Branco AT,Yu S,Lemos B

    更新日期：2014-09-11 00:00:00

  • Distinct CCK-positive SFO neurons are involved in persistent or transient suppression of water intake.

    abstract：:The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. However, the brain mechanisms controlling water intake currently remain unclear. We previously reported that thirst-driving neurons (water neurons) in...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-020-19191-0

    authors： Matsuda T,Hiyama TY,Kobayashi K,Kobayashi K,Noda M

    更新日期：2020-11-10 00:00:00

  • Physical descriptor for the Gibbs energy of inorganic crystalline solids and temperature-dependent materials chemistry.

    abstract：:The Gibbs energy, G, determines the equilibrium conditions of chemical reactions and materials stability. Despite this fundamental and ubiquitous role, G has been tabulated for only a small fraction of known inorganic compounds, impeding a comprehensive perspective on the effects of temperature and composition on mate...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-06682-4

    authors： Bartel CJ,Millican SL,Deml AM,Rumptz JR,Tumas W,Weimer AW,Lany S,Stevanović V,Musgrave CB,Holder AM

    更新日期：2018-10-09 00:00:00

  • NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.

    abstract：:Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a state of unresponsiveness to B cell receptor stimulation. Up to 10% of CLL patients transform from an indolent s...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-017-00830-y

    authors： Märklin M,Heitmann JS,Fuchs AR,Truckenmüller FM,Gutknecht M,Bugl S,Saur SJ,Lazarus J,Kohlhofer U,Quintanilla-Martinez L,Rammensee HG,Salih HR,Kopp HG,Haap M,Kirschniak A,Kanz L,Rao A,Wirths S,Müller MR

    更新日期：2017-10-02 00:00:00

  • Precision ultrasound sensing on a chip.

    abstract：:Ultrasound sensors have wide applications across science and technology. However, improved sensitivity is required for both miniaturisation and increased spatial resolution. Here, we introduce cavity optomechanical ultrasound sensing, where dual optical and mechanical resonances enhance the ultrasound signal. We achie...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-018-08038-4

    authors： Basiri-Esfahani S,Armin A,Forstner S,Bowen WP

    更新日期：2019-01-10 00:00:00

  • Direct cellular delivery of human proteasomes to delay tau aggregation.

    abstract：:The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial to prevent the accumulation of protein aggregate...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms6633

    authors： Han DH,Na HK,Choi WH,Lee JH,Kim YK,Won C,Lee SH,Kim KP,Kuret J,Min DH,Lee MJ

    更新日期：2014-12-05 00:00:00

  • African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin.

    abstract：:A variant at amino acid 47 in human TP53 exists predominantly in individuals of African descent. P47S human and mouse cells show increased cancer risk due to defective ferroptosis. Here, we show that this ferroptotic defect causes iron accumulation in P47S macrophages. This high iron content alters macrophage cytokine...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/s41467-019-14151-9

    authors： Singh KS,Leu JI,Barnoud T,Vonteddu P,Gnanapradeepan K,Lin C,Liu Q,Barton JC,Kossenkov AV,George DL,Murphy ME,Dotiwala F

    更新日期：2020-01-24 00:00:00

  • Central insulin modulates food valuation via mesolimbic pathways.

    abstract：:Central insulin is thought to act at the neural interface between metabolic and hedonic drives to eat. Here, using pharmacological fMRI, we show that intranasal insulin (INI) changes the value of food cues through modulation of mesolimbic pathways. Overnight fasted participants rated the palatability of food pictures ...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms16052

    authors： Tiedemann LJ,Schmid SM,Hettel J,Giesen K,Francke P,Büchel C,Brassen S

    更新日期：2017-07-18 00:00:00

  • The evolutionary origin of human hyper-cooperation.

    abstract：:Proactive, that is, unsolicited, prosociality is a key component of our hyper-cooperation, which in turn has enabled the emergence of various uniquely human traits, including complex cognition, morality and cumulative culture and technology. However, the evolutionary foundation of the human prosocial sentiment remains...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms5747

    authors： Burkart JM,Allon O,Amici F,Fichtel C,Finkenwirth C,Heschl A,Huber J,Isler K,Kosonen ZK,Martins E,Meulman EJ,Richiger R,Rueth K,Spillmann B,Wiesendanger S,van Schaik CP

    更新日期：2014-08-27 00:00:00

  • The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes.

    abstract：:Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a bindin...

    journal_title：Nature communications

    pub_type： 杂志文章

    doi：10.1038/ncomms11482

    authors： Ritterhoff T,Das H,Hofhaus G,Schröder RR,Flotho A,Melchior F

    更新日期：2016-05-10 00:00:00