Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation
Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kα, a medicinal chemistry program has led...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2013-07, Vol.23 (13), p.3741-3748 |
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| container_issue | 13 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Furet, Pascal Guagnano, Vito Fairhurst, Robin A. Imbach-Weese, Patricia Bruce, Ian Knapp, Mark Fritsch, Christine Blasco, Francesca Blanz, Joachim Aichholz, Reiner Hamon, Jacques Fabbro, Doriano Caravatti, Giorgio |
| description | Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kα, a medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719. |
| doi_str_mv | 10.1016/j.bmcl.2013.05.007 |
| format | Article |
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All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-2f6304e6e466543aa35f1ea824946d040dc60322358f35533c8b0db47d213d743</citedby><cites>FETCH-LOGICAL-c479t-2f6304e6e466543aa35f1ea824946d040dc60322358f35533c8b0db47d213d743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2013.05.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23726034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Furet, Pascal</creatorcontrib><creatorcontrib>Guagnano, Vito</creatorcontrib><creatorcontrib>Fairhurst, Robin A.</creatorcontrib><creatorcontrib>Imbach-Weese, Patricia</creatorcontrib><creatorcontrib>Bruce, Ian</creatorcontrib><creatorcontrib>Knapp, Mark</creatorcontrib><creatorcontrib>Fritsch, Christine</creatorcontrib><creatorcontrib>Blasco, Francesca</creatorcontrib><creatorcontrib>Blanz, Joachim</creatorcontrib><creatorcontrib>Aichholz, Reiner</creatorcontrib><creatorcontrib>Hamon, Jacques</creatorcontrib><creatorcontrib>Fabbro, Doriano</creatorcontrib><creatorcontrib>Caravatti, Giorgio</creatorcontrib><title>Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. 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Guagnano, Vito ; Fairhurst, Robin A. ; Imbach-Weese, Patricia ; Bruce, Ian ; Knapp, Mark ; Fritsch, Christine ; Blasco, Francesca ; Blanz, Joachim ; Aichholz, Reiner ; Hamon, Jacques ; Fabbro, Doriano ; Caravatti, Giorgio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-2f6304e6e466543aa35f1ea824946d040dc60322358f35533c8b0db47d213d743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>antineoplastic agents</topic><topic>Antitumor agent</topic><topic>Biological Availability</topic><topic>Cell Line</topic><topic>chemistry</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Discovery</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>phosphatidylinositol 3-kinase</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>PI3K inhibitors</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Structure-Activity Relationship</topic><topic>Thiazoles - chemical synthesis</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Furet, Pascal</creatorcontrib><creatorcontrib>Guagnano, Vito</creatorcontrib><creatorcontrib>Fairhurst, Robin A.</creatorcontrib><creatorcontrib>Imbach-Weese, Patricia</creatorcontrib><creatorcontrib>Bruce, Ian</creatorcontrib><creatorcontrib>Knapp, Mark</creatorcontrib><creatorcontrib>Fritsch, Christine</creatorcontrib><creatorcontrib>Blasco, Francesca</creatorcontrib><creatorcontrib>Blanz, Joachim</creatorcontrib><creatorcontrib>Aichholz, Reiner</creatorcontrib><creatorcontrib>Hamon, Jacques</creatorcontrib><creatorcontrib>Fabbro, Doriano</creatorcontrib><creatorcontrib>Caravatti, Giorgio</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Furet, Pascal</au><au>Guagnano, Vito</au><au>Fairhurst, Robin A.</au><au>Imbach-Weese, Patricia</au><au>Bruce, Ian</au><au>Knapp, Mark</au><au>Fritsch, Christine</au><au>Blasco, Francesca</au><au>Blanz, Joachim</au><au>Aichholz, Reiner</au><au>Hamon, Jacques</au><au>Fabbro, Doriano</au><au>Caravatti, Giorgio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>23</volume><issue>13</issue><spage>3741</spage><epage>3748</epage><pages>3741-3748</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Phosphatidylinositol-3-kinase α (PI3Kα) is a therapeutic target of high interest in anticancer drug research. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2013-07, Vol.23 (13), p.3741-3748 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals antineoplastic agents Antitumor agent Biological Availability Cell Line chemistry Dogs Dose-Response Relationship, Drug Drug Discovery Female Humans Mice Models, Molecular Molecular Structure phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Phosphorylation - drug effects PI3K inhibitors Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Sprague-Dawley Structure-Activity Relationship Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacology |
| title | Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation |
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