In situ click chemistry generation of cyclooxygenase-2 inhibitors View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Atul Bhardwaj, Jatinder Kaur, Melinda Wuest, Frank Wuest

ABSTRACT

Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity. More... »

PAGES

1

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-016-0009-6

DOI

http://dx.doi.org/10.1038/s41467-016-0009-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1083776852

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28232747


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/2008/1115", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Pharmacology and Pharmaceutical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Anti-Inflammatory Agents, Non-Steroidal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carrageenan", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Click Chemistry", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cyclooxygenase 1", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cyclooxygenase 2", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cyclooxygenase 2 Inhibitors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Design", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Edema", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hindlimb", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Kinetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Molecular Docking Simulation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Structure, Secondary", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pyrazoles", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Rats", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Structure-Activity Relationship", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Thermodynamics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Triazoles", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Alberta", 
          "id": "https://www.grid.ac/institutes/grid.17089.37", 
          "name": [
            "Department of Oncology, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, Alberta, Canada", 
            "Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, 8613-114 Street, T6G 2H7, Edmonton, Alberta, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Bhardwaj", 
        "givenName": "Atul", 
        "id": "sg:person.01304170502.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01304170502.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Alberta", 
          "id": "https://www.grid.ac/institutes/grid.17089.37", 
          "name": [
            "Department of Oncology, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, Alberta, Canada", 
            "Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, 8613-114 Street, T6G 2H7, Edmonton, Alberta, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kaur", 
        "givenName": "Jatinder", 
        "id": "sg:person.01236055302.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236055302.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Alberta", 
          "id": "https://www.grid.ac/institutes/grid.17089.37", 
          "name": [
            "Department of Oncology, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, Alberta, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wuest", 
        "givenName": "Melinda", 
        "id": "sg:person.01125555733.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125555733.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Alberta", 
          "id": "https://www.grid.ac/institutes/grid.17089.37", 
          "name": [
            "Department of Oncology, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, Alberta, Canada", 
            "Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, 8613-114 Street, T6G 2H7, Edmonton, Alberta, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wuest", 
        "givenName": "Frank", 
        "id": "sg:person.01310117533.83", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310117533.83"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1021/jm0613166", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001078240"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm0613166", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001078240"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jo300214d", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001854970"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.271.52.33157", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002703800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ja.2009.28", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003457544", 
          "https://doi.org/10.1038/ja.2009.28"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ja.2009.28", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003457544", 
          "https://doi.org/10.1038/ja.2009.28"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/atvbaha.110.207449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003792635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/atvbaha.110.207449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003792635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/atvbaha.110.207449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003792635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13550-016-0192-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005692715", 
          "https://doi.org/10.1186/s13550-016-0192-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13550-016-0192-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005692715", 
          "https://doi.org/10.1186/s13550-016-0192-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.200461580", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006396695"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio781", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007298020", 
          "https://doi.org/10.1038/nchembio781"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio781", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007298020", 
          "https://doi.org/10.1038/nchembio781"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-med-112211-154330", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008810117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.201400135", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009077844"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0402784101", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010733726"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.200502161", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011107907"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.200502161", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011107907"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/17460441.2014.883377", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011891286"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ml400485g", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012231765"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ar200321n", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012514927"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/384644a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012843708", 
          "https://doi.org/10.1038/384644a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012973605", 
          "https://doi.org/10.1038/nrc2809"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012973605", 
          "https://doi.org/10.1038/nrc2809"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-med-011209-153129", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013138726"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.201206281", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013625293"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr400355w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014819001"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.bjp.0702897", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015723024"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja3001858", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015904277"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cmdc.201300355", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021214957"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.162468699", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025880802"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027810626"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027810626"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.biochem.69.1.145", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028055690"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/qsar.200740085", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028293802"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1521-3773(20020715)41:14<2596::aid-anie2596>3.0.co;2-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028820752"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/pr.56.3.3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029530657"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev.pharmtox.011008.145638", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031630927"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.drudis.2016.02.019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031811973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/anie.200601677", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031848058"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ange.201400135", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033308684"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/17460441.1.6.525", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038732830"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-94-007-7359-2_15", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039569735", 
          "https://doi.org/10.1007/978-94-007-7359-2_15"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1521-3773(20020315)41:6<1053::aid-anie1053>3.0.co;2-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041133765"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja046382g", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042215914"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja046382g", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042215914"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cmdc.201100393", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046058589"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsb1196-927", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046402107", 
          "https://doi.org/10.1038/nsb1196-927"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd1034", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046932856", 
          "https://doi.org/10.1038/nrd1034"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd1034", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046932856", 
          "https://doi.org/10.1038/nrd1034"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja508484c", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047213526"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1194/jlr.r800042-jlr200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048956064"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-09-2664", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049309428"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0837397100", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049930155"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr200409f", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051585649"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m112.372243", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052147016"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/b901969n", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052630834"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/b901969n", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052630834"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.critrevonc.2006.01.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052695909"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/qsar.200740112", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053122270"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr2002992", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053785687"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/cr2002992", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053785687"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bc900276b", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055155842"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bc900276b", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055155842"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi026938h", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055196473"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi026938h", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055196473"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja043031t", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055835790"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja043031t", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055835790"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm0402059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055948694"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm0402059", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055948694"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ol052895w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1056247377"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ol052895w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1056247377"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scitranslmed.3003787", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062687440"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/scitranslmed.3008455", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062688294"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/1381612043453117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069165341"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2017-12", 
    "datePublishedReg": "2017-12-01", 
    "description": "Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41467-016-0009-6", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1043282", 
        "issn": [
          "2041-1723"
        ], 
        "name": "Nature Communications", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "In situ click chemistry generation of cyclooxygenase-2 inhibitors", 
    "pagination": "1", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "c3ad2b431fd9174189700ddc8d5b2467a1cfef29f92c3c376427ac7038bfcd0a"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "28232747"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101528555"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41467-016-0009-6"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1083776852"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41467-016-0009-6", 
      "https://app.dimensions.ai/details/publication/pub.1083776852"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T01:03", 
    "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/v90/0000000001_0000000264/records_8697_00000492.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41467-016-0009-6"
  }
]
 

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/s41467-016-0009-6'

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/s41467-016-0009-6'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-016-0009-6'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-016-0009-6'


 

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

356 TRIPLES      21 PREDICATES      108 URIs      42 LITERALS      30 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41467-016-0009-6 schema:about N05b4b6ddd0e548e7b84436e76b78d49c
2 N05f55293fa744231a3a6764c91816ebc
3 N1c88e97de1f845099b712e8360b9475a
4 N1ee406fe15e9486fb270601094c9bafe
5 N2b1ee750adad428a9bd783ca23ded9ce
6 N2d370689f280429e85fb54b4fbdb0d40
7 N593cc3dc3a11406eb36dcd9f9f648013
8 N59635547ec3b4392b994aa51e2c1bac4
9 N5acf0941938e49868907c5587c2869a9
10 N67bfcd2348324572ba8c60e85d781804
11 N6a541a38b5c3479897820bdfdb0ae9dc
12 N6c2b3fe29c0b47a3bfcc99c27677a53e
13 N7817c01ecf134213a4f8b258d346cfec
14 N83e6f72ac1c14b12a84a8c071fdffef1
15 N99749c6a2ae84c82b36db3ae05f35972
16 Naae10ba6c4c44365b72b07d998137787
17 Nac8a8b996fc341f2a1e2e8f1c2a0b3bc
18 Nc7c2ef0af1e24adfbdaeaa65f0581bc7
19 Nf133b3b39417431388cc0cf65c746fad
20 Nfae6be33646c4b919252cb16f29e1f6e
21 Nfe35643bbf984af3aba79d8cd19c2eb4
22 anzsrc-for:11
23 anzsrc-for:1115
24 schema:author N585efc66a5da45e485ba71a68c35fc17
25 schema:citation sg:pub.10.1007/978-94-007-7359-2_15
26 sg:pub.10.1038/384644a0
27 sg:pub.10.1038/ja.2009.28
28 sg:pub.10.1038/nchembio781
29 sg:pub.10.1038/nrc2809
30 sg:pub.10.1038/nrd1034
31 sg:pub.10.1038/nsb1196-927
32 sg:pub.10.1186/s13550-016-0192-9
33 https://doi.org/10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-5
34 https://doi.org/10.1002/1521-3773(20020315)41:6<1053::aid-anie1053>3.0.co;2-4
35 https://doi.org/10.1002/1521-3773(20020715)41:14<2596::aid-anie2596>3.0.co;2-4
36 https://doi.org/10.1002/ange.201400135
37 https://doi.org/10.1002/anie.200461580
38 https://doi.org/10.1002/anie.200502161
39 https://doi.org/10.1002/anie.200601677
40 https://doi.org/10.1002/anie.201206281
41 https://doi.org/10.1002/anie.201400135
42 https://doi.org/10.1002/cmdc.201100393
43 https://doi.org/10.1002/cmdc.201300355
44 https://doi.org/10.1002/qsar.200740085
45 https://doi.org/10.1002/qsar.200740112
46 https://doi.org/10.1016/j.critrevonc.2006.01.003
47 https://doi.org/10.1016/j.drudis.2016.02.019
48 https://doi.org/10.1021/ar200321n
49 https://doi.org/10.1021/bc900276b
50 https://doi.org/10.1021/bi026938h
51 https://doi.org/10.1021/cr2002992
52 https://doi.org/10.1021/cr200409f
53 https://doi.org/10.1021/cr400355w
54 https://doi.org/10.1021/ja043031t
55 https://doi.org/10.1021/ja046382g
56 https://doi.org/10.1021/ja3001858
57 https://doi.org/10.1021/ja508484c
58 https://doi.org/10.1021/jm0402059
59 https://doi.org/10.1021/jm0613166
60 https://doi.org/10.1021/jo300214d
61 https://doi.org/10.1021/ml400485g
62 https://doi.org/10.1021/ol052895w
63 https://doi.org/10.1038/sj.bjp.0702897
64 https://doi.org/10.1039/b901969n
65 https://doi.org/10.1073/pnas.0402784101
66 https://doi.org/10.1073/pnas.0837397100
67 https://doi.org/10.1073/pnas.162468699
68 https://doi.org/10.1074/jbc.271.52.33157
69 https://doi.org/10.1074/jbc.m112.372243
70 https://doi.org/10.1124/pr.56.3.3
71 https://doi.org/10.1126/scitranslmed.3003787
72 https://doi.org/10.1126/scitranslmed.3008455
73 https://doi.org/10.1146/annurev-med-011209-153129
74 https://doi.org/10.1146/annurev-med-112211-154330
75 https://doi.org/10.1146/annurev.biochem.69.1.145
76 https://doi.org/10.1146/annurev.pharmtox.011008.145638
77 https://doi.org/10.1158/0008-5472.can-09-2664
78 https://doi.org/10.1161/atvbaha.110.207449
79 https://doi.org/10.1194/jlr.r800042-jlr200
80 https://doi.org/10.1517/17460441.1.6.525
81 https://doi.org/10.1517/17460441.2014.883377
82 https://doi.org/10.2174/1381612043453117
83 schema:datePublished 2017-12
84 schema:datePublishedReg 2017-12-01
85 schema:description Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.
86 schema:genre research_article
87 schema:inLanguage en
88 schema:isAccessibleForFree true
89 schema:isPartOf N98655b7c262d461eb5d645229d68c3a2
90 Nc870a62718d24da8a8f217a81ad25be6
91 sg:journal.1043282
92 schema:name In situ click chemistry generation of cyclooxygenase-2 inhibitors
93 schema:pagination 1
94 schema:productId N1109e082498f4da8be5426ad4d00f31d
95 N33d561ba28e34591a7e3170dfaa1eac7
96 Na01185ef531c4160bf3472ac740c0756
97 Nb5498291a80f46bc89d54dfafd3a6ccc
98 Ned78dbd1336e475e91d149d33d8b800b
99 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083776852
100 https://doi.org/10.1038/s41467-016-0009-6
101 schema:sdDatePublished 2019-04-11T01:03
102 schema:sdLicense https://scigraph.springernature.com/explorer/license/
103 schema:sdPublisher N1e470cdb4b7141d7971fbb4df77348b6
104 schema:url https://www.nature.com/articles/s41467-016-0009-6
105 sgo:license sg:explorer/license/
106 sgo:sdDataset articles
107 rdf:type schema:ScholarlyArticle
108 N054109fe0ce64320ae46986c0f418f4e rdf:first sg:person.01310117533.83
109 rdf:rest rdf:nil
110 N05b4b6ddd0e548e7b84436e76b78d49c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Carrageenan
112 rdf:type schema:DefinedTerm
113 N05f55293fa744231a3a6764c91816ebc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Molecular Docking Simulation
115 rdf:type schema:DefinedTerm
116 N1109e082498f4da8be5426ad4d00f31d schema:name readcube_id
117 schema:value c3ad2b431fd9174189700ddc8d5b2467a1cfef29f92c3c376427ac7038bfcd0a
118 rdf:type schema:PropertyValue
119 N1c88e97de1f845099b712e8360b9475a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Humans
121 rdf:type schema:DefinedTerm
122 N1e470cdb4b7141d7971fbb4df77348b6 schema:name Springer Nature - SN SciGraph project
123 rdf:type schema:Organization
124 N1ee406fe15e9486fb270601094c9bafe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Triazoles
126 rdf:type schema:DefinedTerm
127 N2b1ee750adad428a9bd783ca23ded9ce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Cyclooxygenase 1
129 rdf:type schema:DefinedTerm
130 N2d370689f280429e85fb54b4fbdb0d40 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Pyrazoles
132 rdf:type schema:DefinedTerm
133 N33d561ba28e34591a7e3170dfaa1eac7 schema:name pubmed_id
134 schema:value 28232747
135 rdf:type schema:PropertyValue
136 N42d3984b1d1f4053afa167db86d63f8f rdf:first sg:person.01125555733.44
137 rdf:rest N054109fe0ce64320ae46986c0f418f4e
138 N585efc66a5da45e485ba71a68c35fc17 rdf:first sg:person.01304170502.71
139 rdf:rest Na09781c564c74af59047820d6859e5bb
140 N593cc3dc3a11406eb36dcd9f9f648013 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Animals
142 rdf:type schema:DefinedTerm
143 N59635547ec3b4392b994aa51e2c1bac4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Kinetics
145 rdf:type schema:DefinedTerm
146 N5acf0941938e49868907c5587c2869a9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name Cyclooxygenase 2
148 rdf:type schema:DefinedTerm
149 N67bfcd2348324572ba8c60e85d781804 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
150 schema:name Click Chemistry
151 rdf:type schema:DefinedTerm
152 N6a541a38b5c3479897820bdfdb0ae9dc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Structure-Activity Relationship
154 rdf:type schema:DefinedTerm
155 N6c2b3fe29c0b47a3bfcc99c27677a53e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Rats
157 rdf:type schema:DefinedTerm
158 N7817c01ecf134213a4f8b258d346cfec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name Edema
160 rdf:type schema:DefinedTerm
161 N83e6f72ac1c14b12a84a8c071fdffef1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Protein Structure, Secondary
163 rdf:type schema:DefinedTerm
164 N98655b7c262d461eb5d645229d68c3a2 schema:issueNumber 1
165 rdf:type schema:PublicationIssue
166 N99749c6a2ae84c82b36db3ae05f35972 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
167 schema:name Female
168 rdf:type schema:DefinedTerm
169 Na01185ef531c4160bf3472ac740c0756 schema:name nlm_unique_id
170 schema:value 101528555
171 rdf:type schema:PropertyValue
172 Na09781c564c74af59047820d6859e5bb rdf:first sg:person.01236055302.51
173 rdf:rest N42d3984b1d1f4053afa167db86d63f8f
174 Naae10ba6c4c44365b72b07d998137787 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Drug Design
176 rdf:type schema:DefinedTerm
177 Nac8a8b996fc341f2a1e2e8f1c2a0b3bc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Hindlimb
179 rdf:type schema:DefinedTerm
180 Nb5498291a80f46bc89d54dfafd3a6ccc schema:name doi
181 schema:value 10.1038/s41467-016-0009-6
182 rdf:type schema:PropertyValue
183 Nc7c2ef0af1e24adfbdaeaa65f0581bc7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Thermodynamics
185 rdf:type schema:DefinedTerm
186 Nc870a62718d24da8a8f217a81ad25be6 schema:volumeNumber 8
187 rdf:type schema:PublicationVolume
188 Ned78dbd1336e475e91d149d33d8b800b schema:name dimensions_id
189 schema:value pub.1083776852
190 rdf:type schema:PropertyValue
191 Nf133b3b39417431388cc0cf65c746fad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name Gene Expression
193 rdf:type schema:DefinedTerm
194 Nfae6be33646c4b919252cb16f29e1f6e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
195 schema:name Anti-Inflammatory Agents, Non-Steroidal
196 rdf:type schema:DefinedTerm
197 Nfe35643bbf984af3aba79d8cd19c2eb4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
198 schema:name Cyclooxygenase 2 Inhibitors
199 rdf:type schema:DefinedTerm
200 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
201 schema:name Medical and Health Sciences
202 rdf:type schema:DefinedTerm
203 anzsrc-for:1115 schema:inDefinedTermSet anzsrc-for:
204 schema:name Pharmacology and Pharmaceutical Sciences
205 rdf:type schema:DefinedTerm
206 sg:journal.1043282 schema:issn 2041-1723
207 schema:name Nature Communications
208 rdf:type schema:Periodical
209 sg:person.01125555733.44 schema:affiliation https://www.grid.ac/institutes/grid.17089.37
210 schema:familyName Wuest
211 schema:givenName Melinda
212 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01125555733.44
213 rdf:type schema:Person
214 sg:person.01236055302.51 schema:affiliation https://www.grid.ac/institutes/grid.17089.37
215 schema:familyName Kaur
216 schema:givenName Jatinder
217 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236055302.51
218 rdf:type schema:Person
219 sg:person.01304170502.71 schema:affiliation https://www.grid.ac/institutes/grid.17089.37
220 schema:familyName Bhardwaj
221 schema:givenName Atul
222 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01304170502.71
223 rdf:type schema:Person
224 sg:person.01310117533.83 schema:affiliation https://www.grid.ac/institutes/grid.17089.37
225 schema:familyName Wuest
226 schema:givenName Frank
227 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310117533.83
228 rdf:type schema:Person
229 sg:pub.10.1007/978-94-007-7359-2_15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039569735
230 https://doi.org/10.1007/978-94-007-7359-2_15
231 rdf:type schema:CreativeWork
232 sg:pub.10.1038/384644a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012843708
233 https://doi.org/10.1038/384644a0
234 rdf:type schema:CreativeWork
235 sg:pub.10.1038/ja.2009.28 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003457544
236 https://doi.org/10.1038/ja.2009.28
237 rdf:type schema:CreativeWork
238 sg:pub.10.1038/nchembio781 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007298020
239 https://doi.org/10.1038/nchembio781
240 rdf:type schema:CreativeWork
241 sg:pub.10.1038/nrc2809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012973605
242 https://doi.org/10.1038/nrc2809
243 rdf:type schema:CreativeWork
244 sg:pub.10.1038/nrd1034 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046932856
245 https://doi.org/10.1038/nrd1034
246 rdf:type schema:CreativeWork
247 sg:pub.10.1038/nsb1196-927 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046402107
248 https://doi.org/10.1038/nsb1196-927
249 rdf:type schema:CreativeWork
250 sg:pub.10.1186/s13550-016-0192-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005692715
251 https://doi.org/10.1186/s13550-016-0192-9
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027810626
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1002/1521-3773(20020315)41:6<1053::aid-anie1053>3.0.co;2-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041133765
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1002/1521-3773(20020715)41:14<2596::aid-anie2596>3.0.co;2-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028820752
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1002/ange.201400135 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033308684
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1002/anie.200461580 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006396695
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1002/anie.200502161 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011107907
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1002/anie.200601677 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031848058
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1002/anie.201206281 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013625293
268 rdf:type schema:CreativeWork
269 https://doi.org/10.1002/anie.201400135 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009077844
270 rdf:type schema:CreativeWork
271 https://doi.org/10.1002/cmdc.201100393 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046058589
272 rdf:type schema:CreativeWork
273 https://doi.org/10.1002/cmdc.201300355 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021214957
274 rdf:type schema:CreativeWork
275 https://doi.org/10.1002/qsar.200740085 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028293802
276 rdf:type schema:CreativeWork
277 https://doi.org/10.1002/qsar.200740112 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053122270
278 rdf:type schema:CreativeWork
279 https://doi.org/10.1016/j.critrevonc.2006.01.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052695909
280 rdf:type schema:CreativeWork
281 https://doi.org/10.1016/j.drudis.2016.02.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031811973
282 rdf:type schema:CreativeWork
283 https://doi.org/10.1021/ar200321n schema:sameAs https://app.dimensions.ai/details/publication/pub.1012514927
284 rdf:type schema:CreativeWork
285 https://doi.org/10.1021/bc900276b schema:sameAs https://app.dimensions.ai/details/publication/pub.1055155842
286 rdf:type schema:CreativeWork
287 https://doi.org/10.1021/bi026938h schema:sameAs https://app.dimensions.ai/details/publication/pub.1055196473
288 rdf:type schema:CreativeWork
289 https://doi.org/10.1021/cr2002992 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053785687
290 rdf:type schema:CreativeWork
291 https://doi.org/10.1021/cr200409f schema:sameAs https://app.dimensions.ai/details/publication/pub.1051585649
292 rdf:type schema:CreativeWork
293 https://doi.org/10.1021/cr400355w schema:sameAs https://app.dimensions.ai/details/publication/pub.1014819001
294 rdf:type schema:CreativeWork
295 https://doi.org/10.1021/ja043031t schema:sameAs https://app.dimensions.ai/details/publication/pub.1055835790
296 rdf:type schema:CreativeWork
297 https://doi.org/10.1021/ja046382g schema:sameAs https://app.dimensions.ai/details/publication/pub.1042215914
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1021/ja3001858 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015904277
300 rdf:type schema:CreativeWork
301 https://doi.org/10.1021/ja508484c schema:sameAs https://app.dimensions.ai/details/publication/pub.1047213526
302 rdf:type schema:CreativeWork
303 https://doi.org/10.1021/jm0402059 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055948694
304 rdf:type schema:CreativeWork
305 https://doi.org/10.1021/jm0613166 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001078240
306 rdf:type schema:CreativeWork
307 https://doi.org/10.1021/jo300214d schema:sameAs https://app.dimensions.ai/details/publication/pub.1001854970
308 rdf:type schema:CreativeWork
309 https://doi.org/10.1021/ml400485g schema:sameAs https://app.dimensions.ai/details/publication/pub.1012231765
310 rdf:type schema:CreativeWork
311 https://doi.org/10.1021/ol052895w schema:sameAs https://app.dimensions.ai/details/publication/pub.1056247377
312 rdf:type schema:CreativeWork
313 https://doi.org/10.1038/sj.bjp.0702897 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015723024
314 rdf:type schema:CreativeWork
315 https://doi.org/10.1039/b901969n schema:sameAs https://app.dimensions.ai/details/publication/pub.1052630834
316 rdf:type schema:CreativeWork
317 https://doi.org/10.1073/pnas.0402784101 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010733726
318 rdf:type schema:CreativeWork
319 https://doi.org/10.1073/pnas.0837397100 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049930155
320 rdf:type schema:CreativeWork
321 https://doi.org/10.1073/pnas.162468699 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025880802
322 rdf:type schema:CreativeWork
323 https://doi.org/10.1074/jbc.271.52.33157 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002703800
324 rdf:type schema:CreativeWork
325 https://doi.org/10.1074/jbc.m112.372243 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052147016
326 rdf:type schema:CreativeWork
327 https://doi.org/10.1124/pr.56.3.3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029530657
328 rdf:type schema:CreativeWork
329 https://doi.org/10.1126/scitranslmed.3003787 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062687440
330 rdf:type schema:CreativeWork
331 https://doi.org/10.1126/scitranslmed.3008455 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062688294
332 rdf:type schema:CreativeWork
333 https://doi.org/10.1146/annurev-med-011209-153129 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013138726
334 rdf:type schema:CreativeWork
335 https://doi.org/10.1146/annurev-med-112211-154330 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008810117
336 rdf:type schema:CreativeWork
337 https://doi.org/10.1146/annurev.biochem.69.1.145 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028055690
338 rdf:type schema:CreativeWork
339 https://doi.org/10.1146/annurev.pharmtox.011008.145638 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031630927
340 rdf:type schema:CreativeWork
341 https://doi.org/10.1158/0008-5472.can-09-2664 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049309428
342 rdf:type schema:CreativeWork
343 https://doi.org/10.1161/atvbaha.110.207449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003792635
344 rdf:type schema:CreativeWork
345 https://doi.org/10.1194/jlr.r800042-jlr200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048956064
346 rdf:type schema:CreativeWork
347 https://doi.org/10.1517/17460441.1.6.525 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038732830
348 rdf:type schema:CreativeWork
349 https://doi.org/10.1517/17460441.2014.883377 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011891286
350 rdf:type schema:CreativeWork
351 https://doi.org/10.2174/1381612043453117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069165341
352 rdf:type schema:CreativeWork
353 https://www.grid.ac/institutes/grid.17089.37 schema:alternateName University of Alberta
354 schema:name Department of Oncology, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, Alberta, Canada
355 Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, 8613-114 Street, T6G 2H7, Edmonton, Alberta, Canada
356 rdf:type schema:Organization
 




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


...