Click chemistry enables preclinical evaluation of targeted epigenetic therapies.
Identifieur interne : 000A21 ( PubMed/Corpus ); précédent : 000A20; suivant : 000A22Click chemistry enables preclinical evaluation of targeted epigenetic therapies.
Auteurs : Dean S. Tyler ; Johanna Vappiani ; Tatiana Ca Eque ; Enid Y N. Lam ; Aoife Ward ; Omer Gilan ; Yih-Chih Chan ; Antje Hienzsch ; Anna Rutkowska ; Thilo Werner ; Anne J. Wagner ; Dave Lugo ; Richard Gregory ; Cesar Ramirez Molina ; Neil Garton ; Christopher R. Wellaway ; Susan Jackson ; Laura Macpherson ; Margarida Figueiredo ; Sabine Stolzenburg ; Charles C. Bell ; Colin House ; Sarah-Jane Dawson ; Edwin D. Hawkins ; Gerard Drewes ; Rab K. Prinjha ; Raphaël Rodriguez ; Paola Grandi ; Mark A. DawsonSource :
- Science (New York, N.Y.) [ 1095-9203 ] ; 2017.
Abstract
The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.
DOI: 10.1126/science.aal2066
PubMed: 28619718
Links to Exploration step
pubmed:28619718Le document en format XML
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<author><name sortKey="Tyler, Dean S" sort="Tyler, Dean S" uniqKey="Tyler D" first="Dean S" last="Tyler">Dean S. Tyler</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Vappiani, Johanna" sort="Vappiani, Johanna" uniqKey="Vappiani J" first="Johanna" last="Vappiani">Johanna Vappiani</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
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<author><name sortKey="Ca Eque, Tatiana" sort="Ca Eque, Tatiana" uniqKey="Ca Eque T" first="Tatiana" last="Ca Eque">Tatiana Ca Eque</name>
<affiliation><nlm:affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</nlm:affiliation>
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<author><name sortKey="Lam, Enid Y N" sort="Lam, Enid Y N" uniqKey="Lam E" first="Enid Y N" last="Lam">Enid Y N. Lam</name>
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<author><name sortKey="Ward, Aoife" sort="Ward, Aoife" uniqKey="Ward A" first="Aoife" last="Ward">Aoife Ward</name>
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<author><name sortKey="Gilan, Omer" sort="Gilan, Omer" uniqKey="Gilan O" first="Omer" last="Gilan">Omer Gilan</name>
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<author><name sortKey="Chan, Yih Chih" sort="Chan, Yih Chih" uniqKey="Chan Y" first="Yih-Chih" last="Chan">Yih-Chih Chan</name>
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<author><name sortKey="Hienzsch, Antje" sort="Hienzsch, Antje" uniqKey="Hienzsch A" first="Antje" last="Hienzsch">Antje Hienzsch</name>
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<author><name sortKey="Rutkowska, Anna" sort="Rutkowska, Anna" uniqKey="Rutkowska A" first="Anna" last="Rutkowska">Anna Rutkowska</name>
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<author><name sortKey="Werner, Thilo" sort="Werner, Thilo" uniqKey="Werner T" first="Thilo" last="Werner">Thilo Werner</name>
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<author><name sortKey="Wagner, Anne J" sort="Wagner, Anne J" uniqKey="Wagner A" first="Anne J" last="Wagner">Anne J. Wagner</name>
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<author><name sortKey="Lugo, Dave" sort="Lugo, Dave" uniqKey="Lugo D" first="Dave" last="Lugo">Dave Lugo</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gregory, Richard" sort="Gregory, Richard" uniqKey="Gregory R" first="Richard" last="Gregory">Richard Gregory</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Ramirez Molina, Cesar" sort="Ramirez Molina, Cesar" uniqKey="Ramirez Molina C" first="Cesar" last="Ramirez Molina">Cesar Ramirez Molina</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Garton, Neil" sort="Garton, Neil" uniqKey="Garton N" first="Neil" last="Garton">Neil Garton</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Wellaway, Christopher R" sort="Wellaway, Christopher R" uniqKey="Wellaway C" first="Christopher R" last="Wellaway">Christopher R. Wellaway</name>
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<author><name sortKey="Jackson, Susan" sort="Jackson, Susan" uniqKey="Jackson S" first="Susan" last="Jackson">Susan Jackson</name>
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<author><name sortKey="Macpherson, Laura" sort="Macpherson, Laura" uniqKey="Macpherson L" first="Laura" last="Macpherson">Laura Macpherson</name>
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</affiliation>
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<author><name sortKey="Figueiredo, Margarida" sort="Figueiredo, Margarida" uniqKey="Figueiredo M" first="Margarida" last="Figueiredo">Margarida Figueiredo</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Stolzenburg, Sabine" sort="Stolzenburg, Sabine" uniqKey="Stolzenburg S" first="Sabine" last="Stolzenburg">Sabine Stolzenburg</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
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<author><name sortKey="Bell, Charles C" sort="Bell, Charles C" uniqKey="Bell C" first="Charles C" last="Bell">Charles C. Bell</name>
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<author><name sortKey="House, Colin" sort="House, Colin" uniqKey="House C" first="Colin" last="House">Colin House</name>
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<author><name sortKey="Dawson, Sarah Jane" sort="Dawson, Sarah Jane" uniqKey="Dawson S" first="Sarah-Jane" last="Dawson">Sarah-Jane Dawson</name>
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</affiliation>
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<author><name sortKey="Hawkins, Edwin D" sort="Hawkins, Edwin D" uniqKey="Hawkins E" first="Edwin D" last="Hawkins">Edwin D. Hawkins</name>
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<author><name sortKey="Drewes, Gerard" sort="Drewes, Gerard" uniqKey="Drewes G" first="Gerard" last="Drewes">Gerard Drewes</name>
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<author><name sortKey="Prinjha, Rab K" sort="Prinjha, Rab K" uniqKey="Prinjha R" first="Rab K" last="Prinjha">Rab K. Prinjha</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Rodriguez, Raphael" sort="Rodriguez, Raphael" uniqKey="Rodriguez R" first="Raphaël" last="Rodriguez">Raphaël Rodriguez</name>
<affiliation><nlm:affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Grandi, Paola" sort="Grandi, Paola" uniqKey="Grandi P" first="Paola" last="Grandi">Paola Grandi</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. paola.x.grandi@gsk.com mark.dawson@petermac.org.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Dawson, Mark A" sort="Dawson, Mark A" uniqKey="Dawson M" first="Mark A" last="Dawson">Mark A. Dawson</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. paola.x.grandi@gsk.com mark.dawson@petermac.org.</nlm:affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Click chemistry enables preclinical evaluation of targeted epigenetic therapies.</title>
<author><name sortKey="Tyler, Dean S" sort="Tyler, Dean S" uniqKey="Tyler D" first="Dean S" last="Tyler">Dean S. Tyler</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Vappiani, Johanna" sort="Vappiani, Johanna" uniqKey="Vappiani J" first="Johanna" last="Vappiani">Johanna Vappiani</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ca Eque, Tatiana" sort="Ca Eque, Tatiana" uniqKey="Ca Eque T" first="Tatiana" last="Ca Eque">Tatiana Ca Eque</name>
<affiliation><nlm:affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lam, Enid Y N" sort="Lam, Enid Y N" uniqKey="Lam E" first="Enid Y N" last="Lam">Enid Y N. Lam</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ward, Aoife" sort="Ward, Aoife" uniqKey="Ward A" first="Aoife" last="Ward">Aoife Ward</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gilan, Omer" sort="Gilan, Omer" uniqKey="Gilan O" first="Omer" last="Gilan">Omer Gilan</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Chan, Yih Chih" sort="Chan, Yih Chih" uniqKey="Chan Y" first="Yih-Chih" last="Chan">Yih-Chih Chan</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hienzsch, Antje" sort="Hienzsch, Antje" uniqKey="Hienzsch A" first="Antje" last="Hienzsch">Antje Hienzsch</name>
<affiliation><nlm:affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rutkowska, Anna" sort="Rutkowska, Anna" uniqKey="Rutkowska A" first="Anna" last="Rutkowska">Anna Rutkowska</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Werner, Thilo" sort="Werner, Thilo" uniqKey="Werner T" first="Thilo" last="Werner">Thilo Werner</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wagner, Anne J" sort="Wagner, Anne J" uniqKey="Wagner A" first="Anne J" last="Wagner">Anne J. Wagner</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lugo, Dave" sort="Lugo, Dave" uniqKey="Lugo D" first="Dave" last="Lugo">Dave Lugo</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gregory, Richard" sort="Gregory, Richard" uniqKey="Gregory R" first="Richard" last="Gregory">Richard Gregory</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ramirez Molina, Cesar" sort="Ramirez Molina, Cesar" uniqKey="Ramirez Molina C" first="Cesar" last="Ramirez Molina">Cesar Ramirez Molina</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Garton, Neil" sort="Garton, Neil" uniqKey="Garton N" first="Neil" last="Garton">Neil Garton</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Wellaway, Christopher R" sort="Wellaway, Christopher R" uniqKey="Wellaway C" first="Christopher R" last="Wellaway">Christopher R. Wellaway</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jackson, Susan" sort="Jackson, Susan" uniqKey="Jackson S" first="Susan" last="Jackson">Susan Jackson</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Macpherson, Laura" sort="Macpherson, Laura" uniqKey="Macpherson L" first="Laura" last="Macpherson">Laura Macpherson</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Figueiredo, Margarida" sort="Figueiredo, Margarida" uniqKey="Figueiredo M" first="Margarida" last="Figueiredo">Margarida Figueiredo</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Stolzenburg, Sabine" sort="Stolzenburg, Sabine" uniqKey="Stolzenburg S" first="Sabine" last="Stolzenburg">Sabine Stolzenburg</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bell, Charles C" sort="Bell, Charles C" uniqKey="Bell C" first="Charles C" last="Bell">Charles C. Bell</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="House, Colin" sort="House, Colin" uniqKey="House C" first="Colin" last="House">Colin House</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Dawson, Sarah Jane" sort="Dawson, Sarah Jane" uniqKey="Dawson S" first="Sarah-Jane" last="Dawson">Sarah-Jane Dawson</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hawkins, Edwin D" sort="Hawkins, Edwin D" uniqKey="Hawkins E" first="Edwin D" last="Hawkins">Edwin D. Hawkins</name>
<affiliation><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Drewes, Gerard" sort="Drewes, Gerard" uniqKey="Drewes G" first="Gerard" last="Drewes">Gerard Drewes</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Prinjha, Rab K" sort="Prinjha, Rab K" uniqKey="Prinjha R" first="Rab K" last="Prinjha">Rab K. Prinjha</name>
<affiliation><nlm:affiliation>Epigenetics Discovery Performance Unit, Immuno-Inflammation Therapy Area Unit, GlaxoSmithKline, Stevenage, UK.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rodriguez, Raphael" sort="Rodriguez, Raphael" uniqKey="Rodriguez R" first="Raphaël" last="Rodriguez">Raphaël Rodriguez</name>
<affiliation><nlm:affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Grandi, Paola" sort="Grandi, Paola" uniqKey="Grandi P" first="Paola" last="Grandi">Paola Grandi</name>
<affiliation><nlm:affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. paola.x.grandi@gsk.com mark.dawson@petermac.org.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Dawson, Mark A" sort="Dawson, Mark A" uniqKey="Dawson M" first="Mark A" last="Dawson">Mark A. Dawson</name>
<affiliation><nlm:affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. paola.x.grandi@gsk.com mark.dawson@petermac.org.</nlm:affiliation>
</affiliation>
</author>
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<front><div type="abstract" xml:lang="en">The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">28619718</PMID>
<DateCreated><Year>2017</Year>
<Month>06</Month>
<Day>16</Day>
</DateCreated>
<DateRevised><Year>2017</Year>
<Month>10</Month>
<Day>18</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-9203</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>356</Volume>
<Issue>6345</Issue>
<PubDate><Year>2017</Year>
<Month>06</Month>
<Day>30</Day>
</PubDate>
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<Title>Science (New York, N.Y.)</Title>
<ISOAbbreviation>Science</ISOAbbreviation>
</Journal>
<ArticleTitle>Click chemistry enables preclinical evaluation of targeted epigenetic therapies.</ArticleTitle>
<Pagination><MedlinePgn>1397-1401</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1126/science.aal2066</ELocationID>
<Abstract><AbstractText>The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.</AbstractText>
<CopyrightInformation>Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tyler</LastName>
<ForeName>Dean S</ForeName>
<Initials>DS</Initials>
<AffiliationInfo><Affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vappiani</LastName>
<ForeName>Johanna</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">0000-0002-6768-1432</Identifier>
<AffiliationInfo><Affiliation>Cellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cañeque</LastName>
<ForeName>Tatiana</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">0000-0002-1110-0643</Identifier>
<AffiliationInfo><Affiliation>Chemical Cell Biology Group, Institut Curie, Paris Sciences et Lettres Research University, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>CNRS UMR3666, 75005 Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>INSERM U1143, 75005 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lam</LastName>
<ForeName>Enid Y N</ForeName>
<Initials>EYN</Initials>
<Identifier Source="ORCID">0000-0001-5843-7836</Identifier>
<AffiliationInfo><Affiliation>Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ward</LastName>
<ForeName>Aoife</ForeName>
<Initials>A</Initials>
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<Initials>N</Initials>
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<Initials>C</Initials>
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<AffiliationInfo><Affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation>
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<AffiliationInfo><Affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.</Affiliation>
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<Initials>G</Initials>
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<Initials>P</Initials>
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<ForeName>Mark A</ForeName>
<Initials>MA</Initials>
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<AffiliationInfo><Affiliation>Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation>
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<AffiliationInfo><Affiliation>Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.</Affiliation>
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<AffiliationInfo><Affiliation>Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.</Affiliation>
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<Day>15</Day>
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<Month>10</Month>
<Day>17</Day>
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<Month>06</Month>
<Day>01</Day>
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<Month>6</Month>
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