当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Identification of a second binding site in the estrogen receptor.

Identification of a second binding site in the estrogen receptor.

Abstract：

:Fluorescence spectrometry data by Tyulmenkov and Klinge (Arch. Biochem. Biophys. 2000, 381, 135-142) suggest the presence of a second binding site in both subtypes ER alpha and ER beta of the estrogen receptor (ER). A cavity previously described as a solvent channel was located in close proximity to the steroid binding site of both ER subtypes. Derivatives of a tetrahydrochrysene (THC) compound, speculated in the literature to bind to a second binding site, were docked successfully in the second sites identified. However, computation of accurate interaction scores indicates preferred binding to the steroid binding site over the second binding site of both ER alpha and ER beta for all THC derivatives. Therefore, binding to this second site is probably not the reason the THC derivatives are agonists on ER alpha and antagonists on ER beta. Most likely, the smaller steroid binding site of ER beta compared to ER alpha and/or the apparent larger flexibility of helix 12 of ER beta make ER beta more readily adopt an antagonist conformation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

van Hoorn WP

doi

10.1021/jm0109661

keywords:

subject

Has Abstract

pub_date

2002-01-31 00:00:00

pages

584-9

issue

3

eissn

0022-2623

issn

1520-4804

pii

jm0109661

journal_volume

45

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Selection of evodiamine as a novel topoisomerase I inhibitor by structure-based virtual screening and hit optimization of evodiamine derivatives as antitumor agents.

    abstract：:Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to the discovery of structurally diverse TopoI inhibitors. From 23 compounds selected by virtual screening, a total of 14 compounds were found to be TopoI in...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100387d

    authors： Dong G,Sheng C,Wang S,Miao Z,Yao J,Zhang W

    更新日期：2010-11-11 00:00:00

  • Synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5, 7-pentoxocanes and 1,2,4,5-tetroxanes.

    abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990014j

    authors： Kim HS,Shibata Y,Wataya Y,Tsuchiya K,Masuyama A,Nojima M

    更新日期：1999-07-15 00:00:00

  • Characterization of the interaction between human alpha-thrombin and methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carboxylate (LY806303) using electrospray mass spectrometry and tandem mass spectrometry.

    abstract：:Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00068a012

    authors： Sall DJ,Kaiser RE Jr

    更新日期：1993-08-06 00:00:00

  • Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines.

    abstract：:Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200903z

    authors： Liu F,Barsyte-Lovejoy D,Allali-Hassani A,He Y,Herold JM,Chen X,Yates CM,Frye SV,Brown PJ,Huang J,Vedadi M,Arrowsmith CH,Jin J

    更新日期：2011-09-08 00:00:00

  • Design and synthesis of propranolol analogues as serotonergic agents.

    abstract：:Serotonin (5-HT) binds with nearly identical affinity at the various central 5-HT binding sites. Few agents bind with selectivity for 5-HT1A sites. The beta-adrenergic antagonist propranolol binds stereoselectively both at 5-HT1A and 5-HT1B sites (with a several-fold selectivity for the latter) and, whereas it is a 5-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00124a021

    authors： Pierson ME,Lyon RA,Titeler M,Schulman SB,Kowalski P,Glennon RA

    更新日期：1989-04-01 00:00:00

  • Synthesis and biological activity of 5'-substituted 5-fluoropyrimidine nucleosides.

    abstract：:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-d...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00350a024

    authors： Ajmera S,Danenberg PV

    更新日期：1982-08-01 00:00:00

  • 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors.

    abstract：:A series of 8-(substituted phenyl) derivatives of theophylline and other 1,3-dialkylxanthines were evaluated for potency and selectivity as antagonists at A1- and A2-adenosine receptors in brain tissue. Theophylline has a similar potency (Ki = 14 microM) at both A1 and A2 receptors. 8-Phenyltheophylline is 25-35-fold ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00382a018

    authors： Daly JW,Padgett W,Shamim MT,Butts-Lamb P,Waters J

    更新日期：1985-04-01 00:00:00

  • Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1.

    abstract：:ERAP1 is an endoplasmic reticulum-resident zinc aminopeptidase that plays an important role in the immune system by trimming peptides for loading onto major histocompatibility complex proteins. Here, we report discovery of the first inhibitors selective for ERAP1 over its paralogues ERAP2 and IRAP. Compound 1 (N-(N-(2...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00293

    authors： Maben Z,Arya R,Rane D,An WF,Metkar S,Hickey M,Bender S,Ali A,Nguyen TT,Evnouchidou I,Schilling R,Stratikos E,Golden J,Stern LJ

    更新日期：2020-01-09 00:00:00

  • Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia.

    abstract：:Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual in...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm2001508

    authors： Helal CJ,Kang Z,Hou X,Pandit J,Chappie TA,Humphrey JM,Marr ES,Fennell KF,Chenard LK,Fox C,Schmidt CJ,Williams RD,Chapin DS,Siuciak J,Lebel L,Menniti F,Cianfrogna J,Fonseca KR,Nelson FR,O'Connor R,MacDougall M,Mc

    更新日期：2011-07-14 00:00:00

  • Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acid: a new class of broad-spectrum antiviral agents.

    abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00381a004

    authors： De Clercq E,Holý A

    更新日期：1985-03-01 00:00:00

  • N-acylphenylalanines and related compounds. A new class of oral hypoglycemic agents.

    abstract：:N-Benzoyl-DL-phenylalanine (1) was found to possess hypoglycemic activity. A series of the analogues of compound 1 were prepared and evaluated for their blood glucose lowering activity. Both the steric effects of the phenylalanine moiety and the effects of variations in the acyl moiety were investigated. This study el...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00119a007

    authors： Shinkai H,Toi K,Kumashiro I,Seto Y,Fukuma M,Dan K,Toyoshima S

    更新日期：1988-11-01 00:00:00

  • Bisphosphonate inhibition of phosphoglycerate kinase: quantitative structure-activity relationship and pharmacophore modeling investigation.

    abstract：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0604833

    authors： Kotsikorou E,Sahota G,Oldfield E

    更新日期：2006-11-16 00:00:00

  • Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin.

    abstract：:A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of suffic...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01457

    authors： Kienle M,Eisenring P,Stoessel B,Horlacher OP,Hasler S,van Colen G,Hartkoorn RC,Vocat A,Cole ST,Altmann KH

    更新日期：2020-02-13 00:00:00

  • Ligand-Based Design of Allosteric Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists.

    abstract：:Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor associated with the pathogenesis of autoimmune diseases. Allosteric inhibition of RORγt is conceptually new, unique for this specific nuclear receptor, and offers advantages over traditional orthosteric inhibition. Here, we report a highly...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01372

    authors： Meijer FA,Doveston RG,de Vries RMJM,Vos GM,Vos AAA,Leysen S,Scheepstra M,Ottmann C,Milroy LG,Brunsveld L

    更新日期：2020-01-09 00:00:00

  • Design, synthesis, and SAR of potent and selective dipeptide-derived inhibitors for dipeptidyl peptidases.

    abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0308803

    authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

    更新日期：2003-11-06 00:00:00

  • Predicting binding modes from free energy calculations.

    abstract：:To produce reliable predictions of bioactive conformations is a major challenge in the field of structure-based inhibitor design and is a requirement for accurate binding free energy predictions with structure-based methods. A series of HIV-1 reverse transcriptase inhibitors was cross-docked using a non-native crystal...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701218j

    authors： Nervall M,Hanspers P,Carlsson J,Boukharta L,Aqvist J

    更新日期：2008-05-08 00:00:00

  • Novel synthesis of the hexahydroimidazo[1,5b]isoquinoline scaffold: application to the synthesis of glucocorticoid receptor modulators.

    abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901551w

    authors： Xiao HY,Wu DR,Malley MF,Gougoutas JZ,Habte SF,Cunningham MD,Somerville JE,Dodd JH,Barrish JC,Nadler SG,Dhar TG

    更新日期：2010-02-11 00:00:00

  • Design, synthesis, and physicochemical and biological characterization of a new iron chelator of the family of hydroxychromenes.

    abstract：:Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalized from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, postis...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm021022u

    authors： Ferrali M,Bambagioni S,Ceccanti A,Donati D,Giorgi G,Fontani M,Laschi F,Zanello P,Casolaro M,Pietrangelo A

    更新日期：2002-12-19 00:00:00

  • Potent HGF/c-Met axis inhibitors from Eucalyptus globulus: the coupling of phloroglucinol and sesquiterpenoid is essential for the activity.

    abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3007454

    authors： Yang SP,Zhang XW,Ai J,Gan LS,Xu JB,Wang Y,Su ZS,Wang L,Ding J,Geng MY,Yue JM

    更新日期：2012-09-27 00:00:00

  • Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton's Tyrosine Kinase (BT

    abstract：:Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01088

    authors： Watterson SH,De Lucca GV,Shi Q,Langevine CM,Liu Q,Batt DG,Beaudoin Bertrand M,Gong H,Dai J,Yip S,Li P,Sun D,Wu DR,Wang C,Zhang Y,Traeger SC,Pattoli MA,Skala S,Cheng L,Obermeier MT,Vickery R,Discenza LN,D'Arien

    更新日期：2016-10-13 00:00:00

  • Novel 99mTc aminobisthiolato/monothiolato "3 + 1" mixed ligand complexes: structure-activity relationships and preliminary in vivo validation as brain blood flow imaging agents.

    abstract：:A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imagin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960273y

    authors： Pirmettis IC,Papadopoulos MS,Chiotellis E

    更新日期：1997-08-01 00:00:00

  • A 1H NMR study of the interactions and conformations of rationally designed brodimoprim analogues in complexes with Lactobacillus casei dihydrofolate reductase.

    abstract：:A consideration of the detailed structural information available from X-ray crystallographic and NMR studies on complexes of dihydrofolate reductase with inhibitors has led to the design of trimethoprim analogues with improved binding properties. Computer graphic techniques have been used to predict which substituent ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00378a025

    authors： Birdsall B,Feeney J,Pascual C,Roberts GC,Kompis I,Then RL,Müller K,Kroehn A

    更新日期：1984-12-01 00:00:00

  • Structurally specific binding of halogenated biphenyls to thyroxine transport protein.

    abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00155a010

    authors： Rickenbacher U,McKinney JD,Oatley SJ,Blake CC

    更新日期：1986-05-01 00:00:00

  • Deconstruction of the α4β2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine.

    abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200834x

    authors： German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

    更新日期：2011-10-27 00:00:00

  • Tri- and Tetrasubstituted Pyridinylimidazoles as Covalent Inhibitors of c-Jun N-Terminal Kinase 3.

    abstract：:The concept of covalent inhibition of c-Jun N-terminal kinase 3 (JNK3) was successfully transferred to our well validated pyridinylimidazole scaffold varying several structural features in order to deduce crucial structure-activity relationships. Joint targeting of the hydrophobic region I and methylation of imidazole...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01180

    authors： Muth F,El-Gokha A,Ansideri F,Eitel M,Döring E,Sievers-Engler A,Lange A,Boeckler FM,Lämmerhofer M,Koch P,Laufer SA

    更新日期：2017-01-26 00:00:00

  • Synthesis of 3-(4-acylaminopiperazin-1-ylalkyl)indoles as potential antihypertensive agents.

    abstract：:A series of 3-(4-acylaminopiperazin-1-ylalkyl)indoles was synthesized and tested for antihypertensive activity. Compounds with no substituents in the indole portion of the molecule were generally most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these several analogues were very p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00221a024

    authors： Glamkowski EJ,Reitano PA,Woodward DL

    更新日期：1977-11-01 00:00:00

  • Development of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors.

    abstract：:A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocryst...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00439

    authors： Bryan MC,Drobnick J,Gobbi A,Kolesnikov A,Chen Y,Rajapaksa N,Ndubaku C,Feng J,Chang W,Francis R,Yu C,Choo EF,DeMent K,Ran Y,An L,Emson C,Huang Z,Sujatha-Bhaskar S,Brightbill H,DiPasquale A,Maher J,Wai J,McKenzi

    更新日期：2019-07-11 00:00:00

  • Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity.

    abstract：:We previously reported that substrates of semicarbazide-sensitive amine oxidase in combination with low concentrations of vanadate exert potent insulin-like effects. Here we performed homology modeling of the catalytic domain of mouse SSAO/VAP-1 and searched through chemical databases to identify novel SSAO substrates...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0499211

    authors： Marti L,Abella A,De La Cruz X,García-Vicente S,Unzeta M,Carpéné C,Palacín M,Testar X,Orozco M,Zorzano A

    更新日期：2004-09-23 00:00:00

  • Novel lead structures for p38 MAP kinase via FieldScreen virtual screening.

    abstract：:p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-e...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801399r

    authors： Cheeseright TJ,Holm M,Lehmann F,Luik S,Göttert M,Melville JL,Laufer S

    更新日期：2009-07-23 00:00:00

  • Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities.

    abstract：:Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3002982

    authors： Hong S,Kim J,Seo JH,Jung KH,Hong SS,Hong S

    更新日期：2012-06-14 00:00:00