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<OAI-PMH schemaLocation=http://www.openarchives.org/OAI/2.0/ http://www.openarchives.org/OAI/2.0/OAI-PMH.xsd> <responseDate>2018-01-15T18:28:17Z</responseDate> <request identifier=oai:HAL:hal-01187307v1 verb=GetRecord metadataPrefix=oai_dc>http://api.archives-ouvertes.fr/oai/hal/</request> <GetRecord> <record> <header> <identifier>oai:HAL:hal-01187307v1</identifier> <datestamp>2018-01-11</datestamp> <setSpec>type:ART</setSpec> <setSpec>subject:sdv</setSpec> <setSpec>collection:UNIV-RENNES1</setSpec> <setSpec>collection:CNRS</setSpec> <setSpec>collection:UNIV-AG</setSpec> <setSpec>collection:ENSC-RENNES</setSpec> <setSpec>collection:IRSET</setSpec> <setSpec>collection:IGDR</setSpec> <setSpec>collection:SCR-PNSCM</setSpec> <setSpec>collection:ISCR</setSpec> <setSpec>collection:IGDR-SIM</setSpec> <setSpec>collection:IFR140</setSpec> <setSpec>collection:UNIV-AMU</setSpec> <setSpec>collection:BIOSIT</setSpec> <setSpec>collection:OSS</setSpec> <setSpec>collection:UR1-SPM</setSpec> <setSpec>collection:INC-CNRS</setSpec> <setSpec>collection:UR1-UFR-SVE</setSpec> <setSpec>collection:UR1-UFR-SPM</setSpec> <setSpec>collection:PAOLI_CALMETTES</setSpec> <setSpec>collection:MARQUIS</setSpec> <setSpec>collection:FNCLCC</setSpec> <setSpec>collection:STATS-UR1</setSpec> <setSpec>collection:ISCR-CORINT</setSpec> <setSpec>collection:UR1-HAL</setSpec> <setSpec>collection:EHESP</setSpec> <setSpec>collection:USPC</setSpec> <setSpec>collection:UR1-SDLM</setSpec> <setSpec>collection:UR1-SDLMJONCH</setSpec> <setSpec>collection:UR1-SDV</setSpec> <setSpec>collection:UNIV-ANGERS</setSpec> </header> <metadata><dc> <publisher>HAL CCSD</publisher> <title lang=en>A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells</title> <creator>Fouque, Amelie</creator> <creator>Delalande, Olivier</creator> <creator>Jean, Mickael</creator> <creator>Castellano, Remy</creator> <creator>Josselin, Emmanuelle</creator> <creator>Malleter, Marine</creator> <creator>Shoji, Kenji F.</creator> <creator>Hung, Mac Dinh</creator> <creator>Rampanarivo, Hariniaina</creator> <creator>Collette, Yves</creator> <creator>Van De Weghe, Pierre</creator> <creator>Legembre, Patrick</creator> <contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor> <contributor>Institut de Génétique et Développement de Rennes (IGDR) ; Université de Rennes 1 (UR1) - Centre National de la Recherche Scientifique (CNRS) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor> <contributor>Institut des Sciences Chimiques de Rennes (ISCR) ; Université de Rennes 1 (UR1) - Ecole Nationale Supérieure de Chimie de Rennes - Institut National des Sciences Appliquées (INSA) - Centre National de la Recherche Scientifique (CNRS)</contributor> <contributor>Centre de Recherche en Cancérologie de Marseille (CRCM) ; Aix Marseille Université (AMU) - Institut Paoli-Calmettes - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)</contributor> <contributor>Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)</contributor> <contributor>Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC) ; Université de Rennes 1 (UR1) - IFR140</contributor> <contributor>Oncogenesis Stress Signaling (OSS) ; Université de Rennes 1 (UR1) - CRLCC Eugène Marquis (CRLCC)</contributor> <description>International audience</description> <source>ISSN: 0022-2623</source> <source>EISSN: 1520-4804</source> <source>Journal of Medicinal Chemistry</source> <publisher>American Chemical Society</publisher> <identifier>hal-01187307</identifier> <identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187307</identifier> <source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187307</source> <source>Journal of Medicinal Chemistry, American Chemical Society, 2015, 58 (16), pp.6559-6573. 〈10.1021/acs.jmedchem.5b00991〉</source> <identifier>DOI : 10.1021/acs.jmedchem.5b00991</identifier> <relation>info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jmedchem.5b00991</relation> <identifier>PUBMED : 26237138</identifier> <relation>info:eu-repo/semantics/altIdentifier/pmid/26237138</relation> <language>en</language> <subject>[SDV] Life Sciences [q-bio]</subject> <type>info:eu-repo/semantics/article</type> <type>Journal articles</type> <description lang=en>Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology</description> <date>2015</date> </dc> </metadata> </record> </GetRecord> </OAI-PMH>