当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Evaluation of in vitro PXR-based assays and in silico modeling approaches for understanding the binding of a structurally diverse set of drugs to PXR.

Evaluation of in vitro PXR-based assays and in silico modeling approaches for understanding the binding of a structurally diverse set of drugs to PXR.

Abstract：

:The pregnane X-receptor (PXR) is a promiscuous nuclear receptor primarily responsible for the induction of genes from the cytochrome P450 3A family. In this study, we used a previously described PXR/SRC tethered protein to establish two in vitro assays for identifying PXR ligands: automated ligand identification system (ALIS) and temperature-dependent circular dichroism (TdCD). Kd values determined by ALIS and TdCD showed good correlations with the EC50 values determined by a PXR luciferase reporter-gene assay for 37 marketed drugs. The same set of compounds was modeled into the PXR ligand-binding domain that takes into consideration the structural variations of five published X-ray structures of PXR-ligand complexes. Major findings from our in silico analysis are as follows. First, the primary determinants for non-binders of PXR are molecular size and shape of the compounds. Low molecular weight (MW<300) compounds were in general found to be non-binders, and those molecules that do not match the shape of the PXR ligand-binding site may also act as a non-binder. Secondly, the favorable hydrophobic interactions, mostly through aromatic π-π interactions, and the presence of suitable hydrogen bond(s) between the compounds and PXR are attributes of strong binders. Thirdly, the structures of the PXR binding domain possess the flexibility that accommodates structurally diverse compounds, while some of the strong binders may also adapt flexible conformations for fitting into the binding site. The results from this study provide a molecular basis for future efforts in reducing/abolishing the PXR-dependent CYP3A4 induction liability.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Xiao L,Nickbarg E,Wang W,Thomas A,Ziebell M,Prosise WW,Lesburg CA,Taremi SS,Gerlach VL,Le HV,Cheng KC

doi

10.1016/j.bcp.2010.12.003

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

669-79

issue

5

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(10)00844-0

journal_volume

81

pub_type

杂志文章

相关文献

BIOCHEMICAL PHARMACOLOGY文献大全
  • Stimulation by chelerythrine of the phosphorylation of the amino acid serine in an approximately 20 kDa protein present in the mitochondrial fraction of the rat retina.

    abstract：:It has been reported that chelerythrine chloride, a benzophenanthridine alkaloid, with a wide variety of biologic effects stimulates the phosphorylation of an approximately 20 kDa protein present in the mitochondrial fraction of the rat retina. It has also been shown previously that both the serine and threonine resid...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(96)00202-x

    authors： Lombardini JB

    更新日期：1996-07-26 00:00:00

  • Fatty acid acylation of mucin by gastric mucosa: effects of sofalcone and sucralfate.

    abstract：:The effects of antiulcer drugs, sofalcone and sucralfate, on the activity of gastric mucosal mucus glycoprotein fatty acyltransferase were investigated. The acyltransferase enzyme, contained in the detergent extracts of the microsomal fraction of rat gastric mucosa, was incubated with the deacylated gastric mucin and ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(87)90644-7

    authors： Slomiany BL,Liau YH,Mizuta K,Slomiany A

    更新日期：1987-10-01 00:00:00

  • Effect of O6-benzylguanine on the sensitivity of human colon tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

    abstract：:A number of trials were conducted to determine the effect of O6-benzylguanine pretreatment on the sensitivity of human colon tumor xenografts to the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). O6-Benzylguanine has been shown to inactivate the DNA repair protein, O6-alkylguanine-DNA alkyltransfera...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(93)90416-t

    authors： Dolan ME,Pegg AE,Moschel RC,Grindey GB

    更新日期：1993-07-20 00:00:00

  • Inhibition of purine catabolism by benzbromarone in isolated rat liver cells. Comparison with allopurinol and probenecid.

    abstract：:Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regula...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(88)90385-1

    authors： Rodilla F,Sanchez-Beltran MJ,Izquierdo R,Gomez-Ruiz MD,Cabo J

    更新日期：1988-10-01 00:00:00

  • Ca2+/calmodulin-dependent protein kinase II regulation by inhibitor 1 of protein phosphatase 1 alleviates necroptosis in high glucose-induced cardiomyocytes injury.

    abstract：:Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays an important role in the cardiovascular system. However, the potential protective role of inhibitor 1 of protein phosphatase 1 (I1PP1), which is able to regulate CaMKII, in high glucose-induced cardiomyocytes injury remains unknown. In the present study, cardi...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2019.02.022

    authors： Sun L,Chen Y,Luo H,Xu M,Meng G,Zhang W

    更新日期：2019-05-01 00:00:00

  • Metabolic profiling of praziquantel enantiomers.

    abstract：:Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2014.05.001

    authors： Wang H,Fang ZZ,Zheng Y,Zhou K,Hu C,Krausz KW,Sun D,Idle JR,Gonzalez FJ

    更新日期：2014-07-15 00:00:00

  • Insight into tartrate inhibition patterns in vitro and in vivo based on cocrystal structure with UDP-glucuronosyltransferase 2B15.

    abstract：:Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), is a crucial substance metabolism and elimination process that mostly occurs in the liver to protect the body from toxic substances and maintain homeostasis. The reaction functions well in a uridine diphosphate glucuronic acid (UDPGA) -dependent manner...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2019.113753

    authors： Zhang L,Zhu L,Qu W,Wu F,Hu M,Xie W,Liu Z,Wang C

    更新日期：2020-02-01 00:00:00

  • Characterisation of multidrug-resistant Ehrlich ascites tumour cells selected in vivo for resistance to etoposide.

    abstract：:An Ehrlich ascites tumour cell line (EHR2) was selected for resistance to etoposide (VP16) by in vivo exposure to this agent. The resulting cell line (EHR2/VP16) was 114.3-, 5.7-, and 4.0-fold resistant to VP16, daunorubicin, and vincristine, respectively. The amount of salt-extractable immunoreactive topoisomerase II...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(00)00338-5

    authors： Nielsen D,Maare C,Eriksen J,Litman T,Friche E,Skovsgaard T

    更新日期：2000-08-01 00:00:00

  • Serine residues in the α4 nicotinic acetylcholine receptor subunit regulate surface α4β2* receptor expression and clustering.

    abstract：BACKGROUND AND PURPOSE:Chronic nicotine exposure upregulates α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The goal of this study was to examine the role of three serine residues in the large cytoplasmic loop of the α4 subunit on α4β2* upregulation in neurons. EXPERIMENTAL APPROACH:Serine residues S33...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2018.11.008

    authors： Zambrano CA,Escobar D,Ramos-Santiago T,Bollinger I,Stitzel J

    更新日期：2019-01-01 00:00:00

  • The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice.

    abstract：:The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E fe...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(96)00869-6

    authors： Yano T,Yano Y,Uchida M,Murakami A,Hagiwara K,Otani S,Ichikawa T

    更新日期：1997-06-01 00:00:00

  • Hydroxychavicol from Piper betle induces apoptosis, cell cycle arrest, and inhibits epithelial-mesenchymal transition in pancreatic cancer cells.

    abstract：:Pancreatic cancer is a major cause of cancer-related mortality around the world. Currently, options for diagnosis and treatment are extremely limited, which culminates in a very high mortality rate. Intensive research spanning more than four decades has met several roadblocks in terms of improvement in overall surviva...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2019.05.025

    authors： Guha Majumdar A,Subramanian M

    更新日期：2019-08-01 00:00:00

  • Angiotensin II promotes pulmonary metastasis of melanoma through the activation of adhesion molecules in vascular endothelial cells.

    abstract：:Hypertension is considered as one of the cancer progressive factors, and often found comorbidity in cancer patients. Renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is well known pressor peptide associated with RAS. Ang II has been reported to acc...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2018.04.012

    authors： Ishikane S,Hosoda H,Nojiri T,Tokudome T,Mizutani T,Miura K,Akitake Y,Kimura T,Imamichi Y,Kawabe S,Toyohira Y,Yanagihara N,Takahashi-Yanaga F,Miyazato M,Miyamoto K,Kangawa K

    更新日期：2018-08-01 00:00:00

  • Induction of G(2)/M phase arrest and apoptosis by a new synthetic anti-cancer agent, DW2282, in promyelocytic leukemia (HL-60) cells.

    abstract：:We studied the effect of DW2282-,[(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indoline-5-sulfonyl-4,5-dihydro-2-imidazolone].hydrochloride], a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. DW2282, a diarylsulfonylu...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(01)00796-1

    authors： Piao W,Yoo J,Lee DK,Hwang HJ,Kim JH

    更新日期：2001-12-01 00:00:00

  • Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

    abstract：:Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side popul...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2012.04.010

    authors： Hegedüs C,Truta-Feles K,Antalffy G,Várady G,Német K,Ozvegy-Laczka C,Kéri G,Orfi L,Szakács G,Settleman J,Váradi A,Sarkadi B

    更新日期：2012-08-01 00:00:00

  • HeLa cell RNA and protein syntheses. Effects of long-term treatment with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB).

    abstract：:The population growth rate of HeLa cells treated with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) in reinforced Eagle's minimum essential medium was directly related to the concentration of fetal bovine serum in the range from 5 to 30%. Control cells proliferated at a maximal rate (doubling time: ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(84)90306-x

    authors： Tamm I

    更新日期：1984-02-15 00:00:00

  • Effect of various amounts of selenium on the metabolism of mercuric chloride in mice.

    abstract：:Male ddY mice were given one injection of (1) mercury (mercuric chloride) simultaneously with various doses of selenium (sodium selenite), (2) mercury alone, or (3) various doses of selenium alone. The interaction between mercury and selenium in the liver and kidneys at 1, 5, 24, 120, and 240 hr after administration w...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(85)90572-6

    authors： Yamamoto I

    更新日期：1985-08-01 00:00:00

  • Eicosapentaenoic acid as a modulator of inflammation. Effect on prostaglandin and leukotriene synthesis.

    abstract：:Products derived from arachidonic acid (AA) via both the cyclo-oxygenase and lipoxygenase pathways play a role in inflammation: prostaglandins (PGs), particularly PGE2, contribute to the formation of oedema, erythema and hyperalgesia whereas leukotriene B4 (LTB4), a product of the 5' lipoxygenase, may modulate the rec...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(86)90246-7

    authors： Terano T,Salmon JA,Higgs GA,Moncada S

    更新日期：1986-03-01 00:00:00

  • The effect of thiopurine drugs on DNA methylation in relation to TPMT expression.

    abstract：:The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2008.07.026

    authors： Hogarth LA,Redfern CP,Teodoridis JM,Hall AG,Anderson H,Case MC,Coulthard SA

    更新日期：2008-10-15 00:00:00

  • A synthesized cationic tetradecapeptide from hornet venom kills bacteria and neutralizes lipopolysaccharide in vivo and in vitro.

    abstract：:Sepsis is a complex clinical syndrome that results from a harmful host response to infection, in which foreign bacteria and lipopolysaccharide (LPS) are potent activators of different immune cells, including monocytes and macrophages. To date, there are currently few effective adjuvant therapies in clinical use except...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2005.04.040

    authors： Yibin G,Jiang Z,Hong Z,Gengfa L,Liangxi W,Guo W,Yongling L

    更新日期：2005-07-15 00:00:00

  • Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro.

    abstract：:Resistance to anti-cancer chemotherapies often leads to regional failure, and can be caused by biochemical and/or physiological mechanisms. Biochemical mechanisms include the overexpression of resistance-conferring proteins. In contrast, physiological resistance involves the tumor microenvironment, and can be caused b...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(03)00467-2

    authors： Mahoney BP,Raghunand N,Baggett B,Gillies RJ

    更新日期：2003-10-01 00:00:00

  • Role of phospholipases A2 in diabetic retinopathy: in vitro and in vivo studies.

    abstract：:Diabetic retinopathy is one of the leading causes of blindness and the most common complication of diabetes with no cure available. We investigated the role of phospholipases A2 (PLA2) in diabetic retinopathy using an in vitro blood-retinal barrier model (BRB) and an in vivo streptozotocin (STZ)-induced diabetic model...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2013.09.008

    authors： Lupo G,Motta C,Giurdanella G,Anfuso CD,Alberghina M,Drago F,Salomone S,Bucolo C

    更新日期：2013-12-01 00:00:00

  • Reduced (+/-)-3,4-methylenedioxymethamphetamine ("Ecstasy") metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro.

    abstract：:"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine or MDMA] is a CNS stimulant, whose use is increasing despite evidence of long-term neurotoxicity. In vitro, the majority of MDMA is demethylenated to (+/-)-3,4-dihydroxymethamphetamine (DHMA) by the polymorphic cytochrome P450 2D6 (CYP2D6). We investigated the demethy...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(02)01028-6

    authors： Ramamoorthy Y,Yu AM,Suh N,Haining RL,Tyndale RF,Sellers EM

    更新日期：2002-06-15 00:00:00

  • Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: molecules, mechanisms and medicine.

    abstract：:Snake venom three-finger α-neurotoxins (α-3FNTx) act on postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction (NMJ) to produce skeletal muscle paralysis. The discovery of the archetypal α-bungarotoxin (α-BgTx), almost six decades ago, exponentially expanded our knowledge of membrane rec...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.bcp.2020.114168

    authors： Nirthanan S

    更新日期：2020-11-01 00:00:00

  • GABAB receptor phosphorylation regulates KCTD12-induced K⁺ current desensitization.

    abstract：:GABAB receptors assemble from GABAB1 and GABAB2 subunits. GABAB2 additionally associates with auxiliary KCTD subunits (named after their K(+) channel tetramerization-domain). GABAB receptors couple to heterotrimeric G-proteins and activate inwardly-rectifying K(+) channels through the βγ subunits released from the G-p...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2014.07.013

    authors： Adelfinger L,Turecek R,Ivankova K,Jensen AA,Moss SJ,Gassmann M,Bettler B

    更新日期：2014-10-01 00:00:00

  • Triangular gold nanoparticles conjugated with peptide ligands: a new class of inhibitor for Candida albicans secreted aspartyl proteinase.

    abstract：:The aim of this study was to find the peptide ligands to inhibit Candida albicans secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300 different peptides, was constructed, and their interaction with Sap2 was separately calculated by molecular dynamic software. Second, 10 peptide ligands with ...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.bcp.2014.05.020

    authors： Jebali A,Hajjar FH,Hekmatimoghaddam S,Kazemi B,De La Fuente JM,Rashidi M

    更新日期：2014-08-15 00:00:00

  • The role of multidrug resistance proteins MRP1, MRP2 and MRP3 in cellular folate homeostasis.

    abstract：:Previously, we reported that the multidrug resistance proteins MRP1, MRP2 and MRP3 confer resistance to therapeutic antifolates by mediating their cellular extrusion. We now determined whether MRPs also play a role in controlling cellular homeostasis of natural folates. In MRP1, MRP2 and MRP3-transfected 2008 human ov...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0006-2952(02)01615-5

    authors： Hooijberg JH,Peters GJ,Assaraf YG,Kathmann I,Priest DG,Bunni MA,Veerman AJ,Scheffer GL,Kaspers GJ,Jansen G

    更新日期：2003-03-01 00:00:00

  • beta-Naphthoflavone-inducible cytochrome P4501A1 activity in liver microsomes of the marine safi fish (Siganus canaliculatus).

    abstract：:The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NAD...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(96)84544-8

    authors： Raza H,Otaiba A,Montague W

    更新日期：1995-10-26 00:00:00

  • Effect of repeated administration of 11-hydroxy-delta 8-tetrahydrocannabinol, an active metabolite of delta 8-tetrahydrocannabinol, on the hepatic microsomal drug-metabolizing enzyme system of mice.

    abstract：:The effects of delta 8-tetrahydrocannabinol (delta 8-THC) and its major and active metabolite, 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC), on the hepatic microsomal drug-metabolizing enzyme system were studied in mice. The repeated administration of 11-OH-delta 8-THC (5 mg/kg/day, i.v.) for 3 or 7 day...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(86)90304-7

    authors： Watanabe K,Arai M,Narimatsu S,Yamamoto I,Yoshimura H

    更新日期：1986-06-01 00:00:00

  • Na(+), K(+)-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death.

    abstract：:The Na(+), K(+)-ATPase is a ubiquitous membrane transport protein in mammalian cells, responsible for establishing and maintaining high K(+) and low Na(+) in the cytoplasm required for normal resting membrane potentials and various cellular activities. The ionic homeostasis maintained by the Na(+), K(+)-ATPase is also...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/s0006-2952(03)00531-8

    authors： Yu SP

    更新日期：2003-10-15 00:00:00

  • Interaction of sanguinarine iminium and alkanolamine form with calf thymus DNA.

    abstract：:The interaction of sanguinarine iminium form (structure I) and sanguinarine alkanolamine form (structure II) with calf thymus DNA has been studied in buffer of pH 5.2 and pH 10.5, respectively, where the physicochemical properties of DNA remain unchanged. The binding of sanguinarine iminium form to DNA is characterize...

    journal_title：Biochemical pharmacology

    pub_type： 杂志文章

    doi：10.1016/0006-2952(94)90510-x

    authors： Sen A,Maiti M

    更新日期：1994-11-29 00:00:00