Selective inhibition of BET bromodomains View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Panagis Filippakopoulos, Jun Qi, Sarah Picaud, Yao Shen, William B. Smith, Oleg Fedorov, Elizabeth M. Morse, Tracey Keates, Tyler T. Hickman, Ildiko Felletar, Martin Philpott, Shonagh Munro, Michael R. McKeown, Yuchuan Wang, Amanda L. Christie, Nathan West, Michael J. Cameron, Brian Schwartz, Tom D. Heightman, Nicholas La Thangue, Christopher A. French, Olaf Wiest, Andrew L. Kung, Stefan Knapp, James E. Bradner

ABSTRACT

Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family. More... »

PAGES

1067

Journal

TITLE

Nature

ISSUE

7327

VOLUME

468

Related Patents

  • Antitumor Agent
  • Bicyclic Bromodomain Inhibitors
  • Pharmaceutical Compositions For Substituted Quinazolinones
  • Benzo [C] Isoxazoloazepine Bromodomain Inhibitors And Uses Thereof
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Inhibitors Of Bromodomains As Modulators Of Gene Expression
  • Heterocyclic Compounds As Bromodomain Inhibitors
  • Substituted Pyrrolo[2,3-C]Pyridines And Pyrazolo[3,4-C]Pyridines As Bet Protein Inhibitors
  • Hydrophobically Tagged Janus Kinase Inhibitors And Uses Thereof
  • Male Contraceptive Compositions And Methods Of Use
  • Therapeutic Compounds And Uses Thereof
  • Diagnostic And Treatment Methods In Subjects Having Or At Risk Of Developing Resistance To Cancer Therapy
  • Taf1 Inhibitors For The Therapy Of Cancer
  • Pyrazolo-Pyrrolidin-4-One Derivatives And Their Use In The Treatment Of Disease
  • Methods For The Treatment Of T-Cell Acute Lymphoblastic Leukemias
  • Differentiation-Induced Cell Population From Which Undifferentiated Cells Have Been Removed, Use Of Same, And Method For Producing Same
  • Compositions Comprising A Brd4 Antagonist And Methods For The Treatment Of Hiv
  • Potent Analogues Of The C-Myc Inhibitor 10074-G5 With Improved Cell Permeability
  • Genome-Wide Method Of Assessing Interactions Between Chemical Entities And Their Target Molecules
  • Compositions And Methods For Treating Leukemia
  • Benzo [C] Isoxazoloazepine Bromodomain Inhibitors And Uses Thereof
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Anti-Inflammatory Agents
  • Pyrazolopyrrolidine Compounds
  • Substituted Pyrrolo[2,3-C]Pyridines And Pyrazolo[3,4-C]Pyridines As Bet Protein Inhibitors
  • Mutant Smoothened And Methods Of Using The Same
  • Bromodomain Inhibitors
  • Pyrazolo[3,4-D]Pyrimidinone Compounds As Inhibitors Of The P53/Mdm2 Interaction
  • Heterocyclic Compounds As Bromodomain Inhibitors
  • Methods Of Treatment Of Human Cytomegalovirus Infection And Diseases With Bromodomain Inhibitors
  • Pyrrolopyrrolone Derivatives And Their Use As Bet Inhibitors
  • Deuterated Derivatives Of A Thienotriazolodiazapine Bromodomain-Containing Protein Inhibitor
  • Substituted Isoquinolinones And Quinazolinones
  • Male Contraceptive Compositions And Methods Of Use
  • Substituted Thienotriazolodiazapines
  • Pyrrolopyrrolidinone Compounds
  • Bromodomain Inhibitors
  • Quinazolinones As Bromodomain Inhibitors
  • 1h-Pyrrolo[2,3,C]Pyridin-7(6h)-Ones And Pyrazolo[3,4-C]Pyridin-7(6h)-Ones As Inhibitors Of Bet Proteins
  • Isoindolone Derivatives
  • Hydrophobically Tagged Small Molecules As Inducers Of Protein Degradation
  • Substituted Bicyclic Compounds As Bromodomain Inhibitors
  • Bromodomain Inhibitors And Uses Thereof
  • Bicyclic Heterocycles As Bet Protein Inhibitors
  • Bromodomain Inhibitors And Uses Thereof
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Methods To Induce Targeted Protein Degradation Through Bifunctional Molecules
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Bone Marrow On X Chromosome Kinase (Bmx) Inhibitors And Uses Thereof
  • Bromodomain Inhibitors And Uses Thereof
  • Benzo [B] Isoxazoloazepine Bromodomain Inhibitors And Uses Thereof
  • Methods Of Downregulating Translocated Oncogene Expression Using Bromodomain Inhibitors
  • 1h-Pyrrolo[2,3-C]Pyridin-7(6h)-Ones And Pyrazolo[3,4-C]Pyridin-7(6h)-Ones As Inhibitors Of Bet Proteins
  • Compositions And Methods For Treating Neoplasia, Inflammatory Disease And Other Disorders
  • Genome-Wide Method Of Assessing Interactions Between Chemical Entities And Their Target Molecules
  • Pyridinone And Pyridazinone Derivatives
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Benzo [B] Isoxazoloazepine Bromodomain Inhibitors And Uses Thereof
  • Cyclic Amines As Bromodomain Inhibitors
  • Biaryl Derivatives As Bromodomain Inhibitors
  • Compositions And Methods For Treating Neoplasia, Inflammatory Disease And Other Disorders
  • Bromodomain Inhibitors And Uses Thereof
  • Methods To Induce Targeted Protein Degradation Through Bifunctional Molecules
  • Substituted Bicyclic Compounds As Bromodomain Inhibitors
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Bromodomain Inhibitors And Uses Thereof
  • Antitumor Agent
  • The Use Of Substituted 2-Phenyl-3h-Quinazolin-4-Ones And Analogs For Inhibiting Bet (Bromodomain And Extra Terminal Domain) Proteins
  • Bromodomain Inhibitors
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Heterocyclic Compounds As Bromodomain Inhibitors
  • Benzo [C] Isoxazoloazepine Bromodomain Inhibitors And Uses Thereof
  • Mutant Smoothened And Methods Of Using The Same
  • Homogenous Thermal Shift Ligand Binding Assay
  • Novel Substituted Bicyclic Compounds As Bromodomain Inhibitors
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Pyrazolopyrrolidine Derivatives And Their Use In The Treatment Of Disease
  • Fusion Proteins And Methods For Identifying Bromodomain Inhibiting Compounds
  • Bromodomain Inhibitors And Uses Thereof
  • Use Of Substituted 2-Phenyl-3h-Quinazolin-4-Ones And Analogs For Inhibiting Bromodomain And Extra Terminal Domain (Bet) Proteins
  • Pyrazolo-Pyrrolidin-4-One Derivatives As Bet Inhibitors And Their Use In The Treatment Of Disease
  • Cyclic Amines As Bromodomain Inhibitors
  • Bromodomain Inhibitors
  • Methods And Compositions For Modulating Frataxin Expression
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Tetrahydroquinoline Compositions As Bet Bromodomain Inhibitors
  • Compositions And Methods For Treating Neoplasia, Inflammatory Disease And Other Disorders
  • Crystalline Forms Of 2-((4s)-6-(4-Chlorophenyl)-1-Methyl-4h-Benzo[C]Isoxazolo[4,5-E]Azepin-4-Yl)Acetamide
  • Janus Kinase Inhibitors And Uses Thereof
  • Method For Modulating Pigmentation By Targeting Bet Bromodomain Proteins
  • Compositions And Methods For The Treatment Of Hiv
  • Bromodomain Inhibitors
  • Pyrazolopyrrolidine Derivatives And Their Use In The Treatment Of Disease
  • Bicyclic Bromodomain Inhibitors
  • Substituted5-(3,5-Dimethylisoxazol-4-Yl)Indoline-2-Ones
  • Methods To Induce Targeted Protein Degradation Through Bifunctional Molecules
  • Bicyclic Heterocycles As Bet Protein Inhibitors
  • Methods And Compositions For Inhibition Of Bromodomain-Containing Proteins
  • Tricyclic Heterocycles As Bet Protein Inhibitors
  • Imidazopyrrolidine Derivatives And Their Use In The Treatment Of Disease
  • Substituted Purinone Compounds
  • Pyrazolopyrrolidine Derivatives And Their Use In The Treatment Of Disease
  • Bicyclic Bromodomain Inhibitors
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09504

    DOI

    http://dx.doi.org/10.1038/nature09504

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001851540

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20871596


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Azirines", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Binding Sites", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carcinoma, Squamous Cell", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Differentiation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Proliferation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chromatin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Dihydropyridines", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Nude", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Molecular", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Nuclear Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Binding", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Structure, Tertiary", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recombinant Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Alignment", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Skin Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Stereoisomerism", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transcription Factors", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Filippakopoulos", 
            "givenName": "Panagis", 
            "id": "sg:person.07544325447.41", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07544325447.41"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Qi", 
            "givenName": "Jun", 
            "id": "sg:person.01272237474.95", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272237474.95"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Picaud", 
            "givenName": "Sarah", 
            "id": "sg:person.01224621600.82", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224621600.82"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Notre Dame", 
              "id": "https://www.grid.ac/institutes/grid.131063.6", 
              "name": [
                "Walther Cancer Research Center and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Shen", 
            "givenName": "Yao", 
            "id": "sg:person.0722472330.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722472330.08"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Smith", 
            "givenName": "William B.", 
            "id": "sg:person.0610253603.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610253603.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fedorov", 
            "givenName": "Oleg", 
            "id": "sg:person.01327374553.06", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327374553.06"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Morse", 
            "givenName": "Elizabeth M.", 
            "id": "sg:person.0624371417.10", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624371417.10"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Keates", 
            "givenName": "Tracey", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Pathology, Brigham & Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hickman", 
            "givenName": "Tyler T.", 
            "id": "sg:person.01214603121.30", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214603121.30"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Felletar", 
            "givenName": "Ildiko", 
            "id": "sg:person.01111401775.55", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01111401775.55"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Philpott", 
            "givenName": "Martin", 
            "id": "sg:person.01065337764.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01065337764.44"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Pharmacology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Munro", 
            "givenName": "Shonagh", 
            "id": "sg:person.01070107441.43", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01070107441.43"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA", 
                "Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "McKeown", 
            "givenName": "Michael R.", 
            "id": "sg:person.0663061774.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0663061774.44"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wang", 
            "givenName": "Yuchuan", 
            "id": "sg:person.010317636157.08", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010317636157.08"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Lurie Family Imaging Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Christie", 
            "givenName": "Amanda L.", 
            "id": "sg:person.01073274407.59", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073274407.59"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "West", 
            "givenName": "Nathan", 
            "id": "sg:person.0610513612.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610513612.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Pathology, Brigham & Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cameron", 
            "givenName": "Michael J.", 
            "id": "sg:person.0607631553.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607631553.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Pathology, Brigham & Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schwartz", 
            "givenName": "Brian", 
            "id": "sg:person.0762465031.40", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762465031.40"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Heightman", 
            "givenName": "Tom D.", 
            "id": "sg:person.0627114123.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627114123.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Pharmacology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "La Thangue", 
            "givenName": "Nicholas", 
            "id": "sg:person.0666527705.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666527705.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Department of Pathology, Brigham & Women\u2019s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "French", 
            "givenName": "Christopher A.", 
            "id": "sg:person.01124043171.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01124043171.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Notre Dame", 
              "id": "https://www.grid.ac/institutes/grid.131063.6", 
              "name": [
                "Walther Cancer Research Center and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wiest", 
            "givenName": "Olaf", 
            "id": "sg:person.01305474424.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305474424.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Dana\u2013Farber Cancer Institute", 
              "id": "https://www.grid.ac/institutes/grid.65499.37", 
              "name": [
                "Lurie Family Imaging Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA", 
                "Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children\u2019s Hospital, Boston, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kung", 
            "givenName": "Andrew L.", 
            "id": "sg:person.01041700036.85", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041700036.85"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Oxford", 
              "id": "https://www.grid.ac/institutes/grid.4991.5", 
              "name": [
                "Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK", 
                "Department of Clinical Pharmacology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Knapp", 
            "givenName": "Stefan", 
            "id": "sg:person.0624726333.55", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624726333.55"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA", 
                "Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bradner", 
            "givenName": "James E.", 
            "id": "sg:person.01002551055.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01002551055.27"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1016/s0002-9440(10)63049-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000646612"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2007.321", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004111620", 
              "https://doi.org/10.1038/nprot.2007.321"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2008-07-168583", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004353616"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/00000421-200306000-00019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005139003"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2005.06.029", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006166314"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2005.06.029", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006166314"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.92.7.2558", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010372506"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.01020-07", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011117404"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkp899", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012872191"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.271.43.27176", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013886599"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.296", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014095415", 
              "https://doi.org/10.1038/nchembio.296"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.296", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014095415", 
              "https://doi.org/10.1038/nchembio.296"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.20.17.6537-6549.2000", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014102176"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.270.21.12335", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015021410"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ddr.430060102", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015735263"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2006.11.002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015832874"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/pas.0b013e318198d666", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016464618"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/pas.0b013e318198d666", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016464618"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/pas.0b013e318198d666", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016464618"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0708800104", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016912541"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio0709-441", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016974153", 
              "https://doi.org/10.1038/nchembio0709-441"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio0709-441", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016974153", 
              "https://doi.org/10.1038/nchembio0709-441"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/jm0504858", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018821078"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/jm0504858", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018821078"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1091/mbc.e09-05-0380", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018849930"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210852", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019992728", 
              "https://doi.org/10.1038/sj.onc.1210852"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.289.5486.1938", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021639730"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208173", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022175796", 
              "https://doi.org/10.1038/sj.onc.1208173"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1208173", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022175796", 
              "https://doi.org/10.1038/sj.onc.1208173"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2010.03.030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022874771"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejm200104053441401", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026812584"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/01.coc.0000020960.98562.84", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030428674"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1097/01.coc.0000020960.98562.84", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030428674"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.12.5.755", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032496652"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.111", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032919195", 
              "https://doi.org/10.1038/nchembio.111"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(02)01196-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034737633"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cub.2009.02.015", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036098073"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m109.033712", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036573220"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.01365-08", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041010787"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.00299-09", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041404072"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jnci/91.2.163", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042748841"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/jvi.00502-06", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044978788"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0014-5793(01)03309-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047051080"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.73.11.3937", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049171581"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm0596-561", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051513257", 
              "https://doi.org/10.1038/nm0596-561"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/emboj/19.22.6141", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052111056"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1075223330", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079589612", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082854607", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2010-12", 
        "datePublishedReg": "2010-12-01", 
        "description": "Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/nature09504", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2753802", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2766919", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2753860", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5134617", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2411184", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1018957", 
            "issn": [
              "0090-0028", 
              "1476-4687"
            ], 
            "name": "Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "7327", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "468"
          }
        ], 
        "name": "Selective inhibition of BET bromodomains", 
        "pagination": "1067", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "08d1d5cf6f8a19de2e4859afa637f930b0da8647ccbaaec817d526d132e11e40"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "20871596"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0410462"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/nature09504"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1001851540"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/nature09504", 
          "https://app.dimensions.ai/details/publication/pub.1001851540"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T10:53", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000351_0000000351/records_43235_00000000.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/nature09504"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature09504'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature09504'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature09504'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature09504'


     

    This table displays all metadata directly associated to this object as RDF triples.

    501 TRIPLES      21 PREDICATES      94 URIs      45 LITERALS      33 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/nature09504 schema:about N0444afd1e9b046d4992758a507f00b0d
    2 N0fdfd91f0fcd4151aa90e0099ce9f879
    3 N105dd54f3a5745f180f221d70cf4b1e8
    4 N1627758068ab477dadb58ee87ca87743
    5 N172f90d3770046e6870cec310a6dad16
    6 N197cfd32c7884d3aa48a236031953233
    7 N1d5485754e8747989264a9cd87aa6951
    8 N282a2b4f153c47e79dfd274d7d0d10c8
    9 N3cfb6a45a260445aa387559c85bd8337
    10 N4381e80138004f2cb3f04d996c751ce8
    11 N4516928e5e28412c838ea3d8833ff708
    12 N4879a1c632054883af16ad9fc6fed929
    13 N5301180aa7a64310acc86ce11e562e80
    14 N90d1c061e7a449eda0eba7bd0f2615d6
    15 N9454b866d0304894beb1eb39ca057143
    16 Nbc70984ff28842c9881ba716f1b6dbfc
    17 Nc04bb80ea2704d6090fb823ab27d3c2b
    18 Nc05905efcae342f9993cc68973c2cb62
    19 Nc0d97a53770148fb934e5b68004d0808
    20 Ncc57cabb734649d2990f75822d1a4892
    21 Nd022c12d22ec4ae084a40d8632e8e787
    22 Nde83cacd24cb4d488ec871e419e5785c
    23 Ne60b0ac541c94b568d80b4326f40e2a6
    24 Nf7737becedbc4a209389cb0c99000b1c
    25 anzsrc-for:06
    26 anzsrc-for:0601
    27 schema:author Nc7273ab0a38a45dea61cd89e840af801
    28 schema:citation sg:pub.10.1038/nchembio.111
    29 sg:pub.10.1038/nchembio.296
    30 sg:pub.10.1038/nchembio0709-441
    31 sg:pub.10.1038/nm0596-561
    32 sg:pub.10.1038/nprot.2007.321
    33 sg:pub.10.1038/sj.onc.1208173
    34 sg:pub.10.1038/sj.onc.1210852
    35 https://app.dimensions.ai/details/publication/pub.1075223330
    36 https://app.dimensions.ai/details/publication/pub.1079589612
    37 https://app.dimensions.ai/details/publication/pub.1082854607
    38 https://doi.org/10.1002/ddr.430060102
    39 https://doi.org/10.1016/j.cell.2010.03.030
    40 https://doi.org/10.1016/j.cub.2009.02.015
    41 https://doi.org/10.1016/j.molcel.2005.06.029
    42 https://doi.org/10.1016/j.molcel.2006.11.002
    43 https://doi.org/10.1016/s0002-9440(10)63049-0
    44 https://doi.org/10.1016/s0014-5793(01)03309-9
    45 https://doi.org/10.1016/s0092-8674(02)01196-0
    46 https://doi.org/10.1021/jm0504858
    47 https://doi.org/10.1056/nejm200104053441401
    48 https://doi.org/10.1073/pnas.0708800104
    49 https://doi.org/10.1073/pnas.73.11.3937
    50 https://doi.org/10.1073/pnas.92.7.2558
    51 https://doi.org/10.1074/jbc.270.21.12335
    52 https://doi.org/10.1074/jbc.271.43.27176
    53 https://doi.org/10.1074/jbc.m109.033712
    54 https://doi.org/10.1091/mbc.e09-05-0380
    55 https://doi.org/10.1093/emboj/19.22.6141
    56 https://doi.org/10.1093/jnci/91.2.163
    57 https://doi.org/10.1093/nar/gkp899
    58 https://doi.org/10.1097/00000421-200306000-00019
    59 https://doi.org/10.1097/01.coc.0000020960.98562.84
    60 https://doi.org/10.1097/pas.0b013e318198d666
    61 https://doi.org/10.1101/gad.12.5.755
    62 https://doi.org/10.1126/science.289.5486.1938
    63 https://doi.org/10.1128/jvi.00502-06
    64 https://doi.org/10.1128/mcb.00299-09
    65 https://doi.org/10.1128/mcb.01020-07
    66 https://doi.org/10.1128/mcb.01365-08
    67 https://doi.org/10.1128/mcb.20.17.6537-6549.2000
    68 https://doi.org/10.1182/blood-2008-07-168583
    69 schema:datePublished 2010-12
    70 schema:datePublishedReg 2010-12-01
    71 schema:description Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.
    72 schema:genre research_article
    73 schema:inLanguage en
    74 schema:isAccessibleForFree true
    75 schema:isPartOf N01281a89b97749e8acf6323de897b668
    76 Ne8aea06d884f47a3ae13ce858e8e39b2
    77 sg:journal.1018957
    78 schema:name Selective inhibition of BET bromodomains
    79 schema:pagination 1067
    80 schema:productId N0c0a46137bf440a79423754341c934f5
    81 N38f3acd0015c4b9e8d990940c9e5a927
    82 N477c0501311845cabb9d3c2260ae1d7a
    83 N740d564783014549ac0cc213f3b13311
    84 Ndf7bff60d2e0418ca410c98c07e39c84
    85 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001851540
    86 https://doi.org/10.1038/nature09504
    87 schema:sdDatePublished 2019-04-11T10:53
    88 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    89 schema:sdPublisher N9490ec158da7469889b8bca2d513671f
    90 schema:url https://www.nature.com/articles/nature09504
    91 sgo:license sg:explorer/license/
    92 sgo:sdDataset articles
    93 rdf:type schema:ScholarlyArticle
    94 N01281a89b97749e8acf6323de897b668 schema:issueNumber 7327
    95 rdf:type schema:PublicationIssue
    96 N02fba43575ba4eb6bf0bc50ace0d784e rdf:first sg:person.01272237474.95
    97 rdf:rest N2d3de6ce143c49e29f4e13e34c831efa
    98 N0444afd1e9b046d4992758a507f00b0d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    99 schema:name Animals
    100 rdf:type schema:DefinedTerm
    101 N09d27ac82b6242cf8cbf8ae88532c8ca rdf:first sg:person.0607631553.20
    102 rdf:rest Ne51e87bcce08405b809179b343ddc002
    103 N0c0a46137bf440a79423754341c934f5 schema:name dimensions_id
    104 schema:value pub.1001851540
    105 rdf:type schema:PropertyValue
    106 N0e2ebffefd1548d7bc2ae303c4c949eb rdf:first sg:person.01073274407.59
    107 rdf:rest N7a82b69621ab41868e9bc73c0b67d46a
    108 N0fdfd91f0fcd4151aa90e0099ce9f879 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    109 schema:name Stereoisomerism
    110 rdf:type schema:DefinedTerm
    111 N105dd54f3a5745f180f221d70cf4b1e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    112 schema:name Molecular Sequence Data
    113 rdf:type schema:DefinedTerm
    114 N1627758068ab477dadb58ee87ca87743 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    115 schema:name Skin Neoplasms
    116 rdf:type schema:DefinedTerm
    117 N1696b589e2534022a8b61ec2fae7665d schema:name Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    118 rdf:type schema:Organization
    119 N172f90d3770046e6870cec310a6dad16 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Chromatin
    121 rdf:type schema:DefinedTerm
    122 N197cfd32c7884d3aa48a236031953233 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name Cell Proliferation
    124 rdf:type schema:DefinedTerm
    125 N1d5485754e8747989264a9cd87aa6951 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Mice, Nude
    127 rdf:type schema:DefinedTerm
    128 N1f56f8e65e984dfd9bb5e9e2b9a2c0f8 rdf:first sg:person.01305474424.00
    129 rdf:rest N834e471dc78e440ba4ee60af3ac6b01d
    130 N202b0f692642422191a15dfb9fff1aa3 schema:name Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    131 rdf:type schema:Organization
    132 N26560d7f81d548c897ee77f2b4e04e81 rdf:first sg:person.01065337764.44
    133 rdf:rest N48aa2fd1ff88464aabd79c3fd5c47465
    134 N282a2b4f153c47e79dfd274d7d0d10c8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name Mice
    136 rdf:type schema:DefinedTerm
    137 N2d3de6ce143c49e29f4e13e34c831efa rdf:first sg:person.01224621600.82
    138 rdf:rest N792a8cddabff446587f44c3af570f5c7
    139 N2f7182abc0ac4828a977b9f2a6087d42 schema:name Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    140 rdf:type schema:Organization
    141 N31f2a309a6ad4ea9ba219126662d5d1c rdf:first sg:person.0666527705.13
    142 rdf:rest Nd2df68103b96461089a285a90b13efe7
    143 N38f3acd0015c4b9e8d990940c9e5a927 schema:name doi
    144 schema:value 10.1038/nature09504
    145 rdf:type schema:PropertyValue
    146 N3b06510ba2564a8bae2c9f73a85aa89c rdf:first sg:person.0624726333.55
    147 rdf:rest Nec2b7415ec56424e9806dbc0f40bfab4
    148 N3cfb6a45a260445aa387559c85bd8337 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Recombinant Proteins
    150 rdf:type schema:DefinedTerm
    151 N4381e80138004f2cb3f04d996c751ce8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Nuclear Proteins
    153 rdf:type schema:DefinedTerm
    154 N4516928e5e28412c838ea3d8833ff708 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Amino Acid Sequence
    156 rdf:type schema:DefinedTerm
    157 N477c0501311845cabb9d3c2260ae1d7a schema:name nlm_unique_id
    158 schema:value 0410462
    159 rdf:type schema:PropertyValue
    160 N4879a1c632054883af16ad9fc6fed929 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    161 schema:name Carcinoma, Squamous Cell
    162 rdf:type schema:DefinedTerm
    163 N48aa2fd1ff88464aabd79c3fd5c47465 rdf:first sg:person.01070107441.43
    164 rdf:rest Nbd4086aa15cb467f8116643d5eb8bf23
    165 N5024fd413a00497bb1c9238b8cc99fc2 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    166 schema:familyName Keates
    167 schema:givenName Tracey
    168 rdf:type schema:Person
    169 N5301180aa7a64310acc86ce11e562e80 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    170 schema:name Protein Binding
    171 rdf:type schema:DefinedTerm
    172 N583270efb7984fbb9ed1421b38630e46 rdf:first sg:person.0610253603.25
    173 rdf:rest N8b93b3e2edf2454eaa878b39d5ef29f0
    174 N5ee79fbd23934820ba28ca2da838bd38 rdf:first sg:person.01111401775.55
    175 rdf:rest N26560d7f81d548c897ee77f2b4e04e81
    176 N60cb923f35e0409983204c67df02d870 rdf:first sg:person.0624371417.10
    177 rdf:rest N8bc03834777d435591e076819c4772cc
    178 N637a77aa76e640e69cfad54265bc1510 schema:name Lurie Family Imaging Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    179 rdf:type schema:Organization
    180 N6d536fd3a44b4da48dae7e04fe28b8cf rdf:first sg:person.0627114123.05
    181 rdf:rest N31f2a309a6ad4ea9ba219126662d5d1c
    182 N740d564783014549ac0cc213f3b13311 schema:name pubmed_id
    183 schema:value 20871596
    184 rdf:type schema:PropertyValue
    185 N792a8cddabff446587f44c3af570f5c7 rdf:first sg:person.0722472330.08
    186 rdf:rest N583270efb7984fbb9ed1421b38630e46
    187 N7a82b69621ab41868e9bc73c0b67d46a rdf:first sg:person.0610513612.46
    188 rdf:rest N09d27ac82b6242cf8cbf8ae88532c8ca
    189 N834e471dc78e440ba4ee60af3ac6b01d rdf:first sg:person.01041700036.85
    190 rdf:rest N3b06510ba2564a8bae2c9f73a85aa89c
    191 N8b93b3e2edf2454eaa878b39d5ef29f0 rdf:first sg:person.01327374553.06
    192 rdf:rest N60cb923f35e0409983204c67df02d870
    193 N8bc03834777d435591e076819c4772cc rdf:first N5024fd413a00497bb1c9238b8cc99fc2
    194 rdf:rest N90344b8b4a4740cb9046abd8f3622d8c
    195 N90344b8b4a4740cb9046abd8f3622d8c rdf:first sg:person.01214603121.30
    196 rdf:rest N5ee79fbd23934820ba28ca2da838bd38
    197 N90d1c061e7a449eda0eba7bd0f2615d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    198 schema:name Female
    199 rdf:type schema:DefinedTerm
    200 N9454b866d0304894beb1eb39ca057143 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    201 schema:name Cell Line, Tumor
    202 rdf:type schema:DefinedTerm
    203 N9490ec158da7469889b8bca2d513671f schema:name Springer Nature - SN SciGraph project
    204 rdf:type schema:Organization
    205 Na92fb65e51ff4fa096e747f6a23579bd schema:name Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    206 rdf:type schema:Organization
    207 Nb4b09505fdb54449ba37d76b0b84aa47 schema:name Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    208 rdf:type schema:Organization
    209 Nbc70984ff28842c9881ba716f1b6dbfc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    210 schema:name Binding Sites
    211 rdf:type schema:DefinedTerm
    212 Nbd4086aa15cb467f8116643d5eb8bf23 rdf:first sg:person.0663061774.44
    213 rdf:rest Nf33cec3b7e48461ba0254aa221e594e8
    214 Nc04bb80ea2704d6090fb823ab27d3c2b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    215 schema:name Models, Molecular
    216 rdf:type schema:DefinedTerm
    217 Nc05905efcae342f9993cc68973c2cb62 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    218 schema:name Protein Structure, Tertiary
    219 rdf:type schema:DefinedTerm
    220 Nc0d97a53770148fb934e5b68004d0808 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    221 schema:name Humans
    222 rdf:type schema:DefinedTerm
    223 Nc21331dc1900467783ba58c8987bf85d schema:name Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    224 rdf:type schema:Organization
    225 Nc7273ab0a38a45dea61cd89e840af801 rdf:first sg:person.07544325447.41
    226 rdf:rest N02fba43575ba4eb6bf0bc50ace0d784e
    227 Nc86a2c46f53d4df49713f1015c8a40e1 schema:name Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    228 rdf:type schema:Organization
    229 Ncc57cabb734649d2990f75822d1a4892 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    230 schema:name Azirines
    231 rdf:type schema:DefinedTerm
    232 Nd022c12d22ec4ae084a40d8632e8e787 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    233 schema:name Transcription Factors
    234 rdf:type schema:DefinedTerm
    235 Nd2df68103b96461089a285a90b13efe7 rdf:first sg:person.01124043171.24
    236 rdf:rest N1f56f8e65e984dfd9bb5e9e2b9a2c0f8
    237 Nd66d146252e2415d832d02525bee9359 schema:name Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    238 rdf:type schema:Organization
    239 Nde83cacd24cb4d488ec871e419e5785c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    240 schema:name Sequence Alignment
    241 rdf:type schema:DefinedTerm
    242 Ndf7bff60d2e0418ca410c98c07e39c84 schema:name readcube_id
    243 schema:value 08d1d5cf6f8a19de2e4859afa637f930b0da8647ccbaaec817d526d132e11e40
    244 rdf:type schema:PropertyValue
    245 Ne3941d38db384bb196b053a28a3f734a schema:name Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    246 rdf:type schema:Organization
    247 Ne51e87bcce08405b809179b343ddc002 rdf:first sg:person.0762465031.40
    248 rdf:rest N6d536fd3a44b4da48dae7e04fe28b8cf
    249 Ne60b0ac541c94b568d80b4326f40e2a6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    250 schema:name Dihydropyridines
    251 rdf:type schema:DefinedTerm
    252 Ne8aea06d884f47a3ae13ce858e8e39b2 schema:volumeNumber 468
    253 rdf:type schema:PublicationVolume
    254 Nec2b7415ec56424e9806dbc0f40bfab4 rdf:first sg:person.01002551055.27
    255 rdf:rest rdf:nil
    256 Nf33cec3b7e48461ba0254aa221e594e8 rdf:first sg:person.010317636157.08
    257 rdf:rest N0e2ebffefd1548d7bc2ae303c4c949eb
    258 Nf7737becedbc4a209389cb0c99000b1c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    259 schema:name Cell Differentiation
    260 rdf:type schema:DefinedTerm
    261 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    262 schema:name Biological Sciences
    263 rdf:type schema:DefinedTerm
    264 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    265 schema:name Biochemistry and Cell Biology
    266 rdf:type schema:DefinedTerm
    267 sg:grant.2411184 http://pending.schema.org/fundedItem sg:pub.10.1038/nature09504
    268 rdf:type schema:MonetaryGrant
    269 sg:grant.2753802 http://pending.schema.org/fundedItem sg:pub.10.1038/nature09504
    270 rdf:type schema:MonetaryGrant
    271 sg:grant.2753860 http://pending.schema.org/fundedItem sg:pub.10.1038/nature09504
    272 rdf:type schema:MonetaryGrant
    273 sg:grant.2766919 http://pending.schema.org/fundedItem sg:pub.10.1038/nature09504
    274 rdf:type schema:MonetaryGrant
    275 sg:grant.5134617 http://pending.schema.org/fundedItem sg:pub.10.1038/nature09504
    276 rdf:type schema:MonetaryGrant
    277 sg:journal.1018957 schema:issn 0090-0028
    278 1476-4687
    279 schema:name Nature
    280 rdf:type schema:Periodical
    281 sg:person.01002551055.27 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    282 schema:familyName Bradner
    283 schema:givenName James E.
    284 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01002551055.27
    285 rdf:type schema:Person
    286 sg:person.010317636157.08 schema:affiliation N1696b589e2534022a8b61ec2fae7665d
    287 schema:familyName Wang
    288 schema:givenName Yuchuan
    289 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010317636157.08
    290 rdf:type schema:Person
    291 sg:person.01041700036.85 schema:affiliation https://www.grid.ac/institutes/grid.65499.37
    292 schema:familyName Kung
    293 schema:givenName Andrew L.
    294 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01041700036.85
    295 rdf:type schema:Person
    296 sg:person.01065337764.44 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    297 schema:familyName Philpott
    298 schema:givenName Martin
    299 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01065337764.44
    300 rdf:type schema:Person
    301 sg:person.01070107441.43 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    302 schema:familyName Munro
    303 schema:givenName Shonagh
    304 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01070107441.43
    305 rdf:type schema:Person
    306 sg:person.01073274407.59 schema:affiliation N637a77aa76e640e69cfad54265bc1510
    307 schema:familyName Christie
    308 schema:givenName Amanda L.
    309 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073274407.59
    310 rdf:type schema:Person
    311 sg:person.01111401775.55 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    312 schema:familyName Felletar
    313 schema:givenName Ildiko
    314 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01111401775.55
    315 rdf:type schema:Person
    316 sg:person.01124043171.24 schema:affiliation Nc86a2c46f53d4df49713f1015c8a40e1
    317 schema:familyName French
    318 schema:givenName Christopher A.
    319 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01124043171.24
    320 rdf:type schema:Person
    321 sg:person.01214603121.30 schema:affiliation N2f7182abc0ac4828a977b9f2a6087d42
    322 schema:familyName Hickman
    323 schema:givenName Tyler T.
    324 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214603121.30
    325 rdf:type schema:Person
    326 sg:person.01224621600.82 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    327 schema:familyName Picaud
    328 schema:givenName Sarah
    329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224621600.82
    330 rdf:type schema:Person
    331 sg:person.01272237474.95 schema:affiliation N202b0f692642422191a15dfb9fff1aa3
    332 schema:familyName Qi
    333 schema:givenName Jun
    334 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272237474.95
    335 rdf:type schema:Person
    336 sg:person.01305474424.00 schema:affiliation https://www.grid.ac/institutes/grid.131063.6
    337 schema:familyName Wiest
    338 schema:givenName Olaf
    339 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305474424.00
    340 rdf:type schema:Person
    341 sg:person.01327374553.06 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    342 schema:familyName Fedorov
    343 schema:givenName Oleg
    344 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01327374553.06
    345 rdf:type schema:Person
    346 sg:person.0607631553.20 schema:affiliation Na92fb65e51ff4fa096e747f6a23579bd
    347 schema:familyName Cameron
    348 schema:givenName Michael J.
    349 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0607631553.20
    350 rdf:type schema:Person
    351 sg:person.0610253603.25 schema:affiliation Nd66d146252e2415d832d02525bee9359
    352 schema:familyName Smith
    353 schema:givenName William B.
    354 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610253603.25
    355 rdf:type schema:Person
    356 sg:person.0610513612.46 schema:affiliation Nc21331dc1900467783ba58c8987bf85d
    357 schema:familyName West
    358 schema:givenName Nathan
    359 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610513612.46
    360 rdf:type schema:Person
    361 sg:person.0624371417.10 schema:affiliation Ne3941d38db384bb196b053a28a3f734a
    362 schema:familyName Morse
    363 schema:givenName Elizabeth M.
    364 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624371417.10
    365 rdf:type schema:Person
    366 sg:person.0624726333.55 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    367 schema:familyName Knapp
    368 schema:givenName Stefan
    369 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624726333.55
    370 rdf:type schema:Person
    371 sg:person.0627114123.05 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    372 schema:familyName Heightman
    373 schema:givenName Tom D.
    374 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0627114123.05
    375 rdf:type schema:Person
    376 sg:person.0663061774.44 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    377 schema:familyName McKeown
    378 schema:givenName Michael R.
    379 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0663061774.44
    380 rdf:type schema:Person
    381 sg:person.0666527705.13 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    382 schema:familyName La Thangue
    383 schema:givenName Nicholas
    384 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666527705.13
    385 rdf:type schema:Person
    386 sg:person.0722472330.08 schema:affiliation https://www.grid.ac/institutes/grid.131063.6
    387 schema:familyName Shen
    388 schema:givenName Yao
    389 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722472330.08
    390 rdf:type schema:Person
    391 sg:person.07544325447.41 schema:affiliation https://www.grid.ac/institutes/grid.4991.5
    392 schema:familyName Filippakopoulos
    393 schema:givenName Panagis
    394 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07544325447.41
    395 rdf:type schema:Person
    396 sg:person.0762465031.40 schema:affiliation Nb4b09505fdb54449ba37d76b0b84aa47
    397 schema:familyName Schwartz
    398 schema:givenName Brian
    399 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762465031.40
    400 rdf:type schema:Person
    401 sg:pub.10.1038/nchembio.111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032919195
    402 https://doi.org/10.1038/nchembio.111
    403 rdf:type schema:CreativeWork
    404 sg:pub.10.1038/nchembio.296 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014095415
    405 https://doi.org/10.1038/nchembio.296
    406 rdf:type schema:CreativeWork
    407 sg:pub.10.1038/nchembio0709-441 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016974153
    408 https://doi.org/10.1038/nchembio0709-441
    409 rdf:type schema:CreativeWork
    410 sg:pub.10.1038/nm0596-561 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051513257
    411 https://doi.org/10.1038/nm0596-561
    412 rdf:type schema:CreativeWork
    413 sg:pub.10.1038/nprot.2007.321 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004111620
    414 https://doi.org/10.1038/nprot.2007.321
    415 rdf:type schema:CreativeWork
    416 sg:pub.10.1038/sj.onc.1208173 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022175796
    417 https://doi.org/10.1038/sj.onc.1208173
    418 rdf:type schema:CreativeWork
    419 sg:pub.10.1038/sj.onc.1210852 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019992728
    420 https://doi.org/10.1038/sj.onc.1210852
    421 rdf:type schema:CreativeWork
    422 https://app.dimensions.ai/details/publication/pub.1075223330 schema:CreativeWork
    423 https://app.dimensions.ai/details/publication/pub.1079589612 schema:CreativeWork
    424 https://app.dimensions.ai/details/publication/pub.1082854607 schema:CreativeWork
    425 https://doi.org/10.1002/ddr.430060102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015735263
    426 rdf:type schema:CreativeWork
    427 https://doi.org/10.1016/j.cell.2010.03.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022874771
    428 rdf:type schema:CreativeWork
    429 https://doi.org/10.1016/j.cub.2009.02.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036098073
    430 rdf:type schema:CreativeWork
    431 https://doi.org/10.1016/j.molcel.2005.06.029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006166314
    432 rdf:type schema:CreativeWork
    433 https://doi.org/10.1016/j.molcel.2006.11.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015832874
    434 rdf:type schema:CreativeWork
    435 https://doi.org/10.1016/s0002-9440(10)63049-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000646612
    436 rdf:type schema:CreativeWork
    437 https://doi.org/10.1016/s0014-5793(01)03309-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047051080
    438 rdf:type schema:CreativeWork
    439 https://doi.org/10.1016/s0092-8674(02)01196-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034737633
    440 rdf:type schema:CreativeWork
    441 https://doi.org/10.1021/jm0504858 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018821078
    442 rdf:type schema:CreativeWork
    443 https://doi.org/10.1056/nejm200104053441401 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026812584
    444 rdf:type schema:CreativeWork
    445 https://doi.org/10.1073/pnas.0708800104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016912541
    446 rdf:type schema:CreativeWork
    447 https://doi.org/10.1073/pnas.73.11.3937 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049171581
    448 rdf:type schema:CreativeWork
    449 https://doi.org/10.1073/pnas.92.7.2558 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010372506
    450 rdf:type schema:CreativeWork
    451 https://doi.org/10.1074/jbc.270.21.12335 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015021410
    452 rdf:type schema:CreativeWork
    453 https://doi.org/10.1074/jbc.271.43.27176 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013886599
    454 rdf:type schema:CreativeWork
    455 https://doi.org/10.1074/jbc.m109.033712 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036573220
    456 rdf:type schema:CreativeWork
    457 https://doi.org/10.1091/mbc.e09-05-0380 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018849930
    458 rdf:type schema:CreativeWork
    459 https://doi.org/10.1093/emboj/19.22.6141 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052111056
    460 rdf:type schema:CreativeWork
    461 https://doi.org/10.1093/jnci/91.2.163 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042748841
    462 rdf:type schema:CreativeWork
    463 https://doi.org/10.1093/nar/gkp899 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012872191
    464 rdf:type schema:CreativeWork
    465 https://doi.org/10.1097/00000421-200306000-00019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005139003
    466 rdf:type schema:CreativeWork
    467 https://doi.org/10.1097/01.coc.0000020960.98562.84 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030428674
    468 rdf:type schema:CreativeWork
    469 https://doi.org/10.1097/pas.0b013e318198d666 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016464618
    470 rdf:type schema:CreativeWork
    471 https://doi.org/10.1101/gad.12.5.755 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032496652
    472 rdf:type schema:CreativeWork
    473 https://doi.org/10.1126/science.289.5486.1938 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021639730
    474 rdf:type schema:CreativeWork
    475 https://doi.org/10.1128/jvi.00502-06 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044978788
    476 rdf:type schema:CreativeWork
    477 https://doi.org/10.1128/mcb.00299-09 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041404072
    478 rdf:type schema:CreativeWork
    479 https://doi.org/10.1128/mcb.01020-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011117404
    480 rdf:type schema:CreativeWork
    481 https://doi.org/10.1128/mcb.01365-08 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041010787
    482 rdf:type schema:CreativeWork
    483 https://doi.org/10.1128/mcb.20.17.6537-6549.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014102176
    484 rdf:type schema:CreativeWork
    485 https://doi.org/10.1182/blood-2008-07-168583 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004353616
    486 rdf:type schema:CreativeWork
    487 https://www.grid.ac/institutes/grid.131063.6 schema:alternateName University of Notre Dame
    488 schema:name Walther Cancer Research Center and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA
    489 rdf:type schema:Organization
    490 https://www.grid.ac/institutes/grid.38142.3c schema:alternateName Harvard University
    491 schema:name Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    492 Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
    493 rdf:type schema:Organization
    494 https://www.grid.ac/institutes/grid.4991.5 schema:alternateName University of Oxford
    495 schema:name Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    496 Department of Clinical Pharmacology, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    497 rdf:type schema:Organization
    498 https://www.grid.ac/institutes/grid.65499.37 schema:alternateName Dana–Farber Cancer Institute
    499 schema:name Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children’s Hospital, Boston, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    500 Lurie Family Imaging Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    501 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...