Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms
Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl‐substituted analogues were further derivatized as prodrugs resulting in...
Gespeichert in:
| Veröffentlicht in: | ChemMedChem 2013-06, Vol.8 (6), p.914-918 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 918 |
|---|---|
| container_issue | 6 |
| container_start_page | 914 |
| container_title | ChemMedChem |
| container_volume | 8 |
| creator | O'Brien, Nathan J. Amran, Syazwani Medan, Jelena Cleary, Ben Deady, Leslie W. Jennings, Ian G. Thompson, Philip E. Abbott, Belinda M. |
| description | Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl‐substituted analogues were further derivatized as prodrugs resulting in restoration of cell‐based activity. These data provide a conceptual model for development of tumor‐targeting prodrug forms of cell‐impermeable PI3K inhibitors. |
| doi_str_mv | 10.1002/cmdc.201200583 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1356369696</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1356369696</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2283-61ecd7e1d463b84840882aa22771de42c6800ed26d446d4b3fadd75b909710b43</originalsourceid><addsrcrecordid>eNqFkE9v1DAQxS1ERUvhyhH5WA7Z-l9i51ht6bJ0S_cA6tFy4gkxJPHWzgK5cYAvyiepV1tW3NBoNCPP7z1ZD6FXlMwoIey87m09Y4QyQnLFn6ATqgqSSark08Muy2P0PMYvhAihqHqGjhnPCyXy_AT9WvsRhhEvh9ZVbvQhYt_gdevjpjWjs1PnBh_Tofvz8zfHZ-slf4Ov3WAi4DERuDXfAF8Mo9sE37kGQlLtXuo03Djh26Gb8F0LA76ELl0CWGwiXgdvw_YzvvKhjy_QUWO6CC8f5yn6dPX24_xdtrpdLOcXq6xmTPGsoFBbCdSKgldKKEGUYsYwJiW1IFhdKELAssIKkbrijbFW5lVJSklJJfgpOtv7pr_ebyGOunexhq4zA_ht1DTFwosyVUJne7QOPsYAjd4E15swaUr0Lnm9S14fkk-C14_e26oHe8D_Rp2Acg98dx1M_7HT85vL-b_m2V7r4gg_DloTvupCcpnruw8Lnd8QsViV7_WCPwBgMaCO</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1356369696</pqid></control><display><type>article</type><title>Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>O'Brien, Nathan J. ; Amran, Syazwani ; Medan, Jelena ; Cleary, Ben ; Deady, Leslie W. ; Jennings, Ian G. ; Thompson, Philip E. ; Abbott, Belinda M.</creator><creatorcontrib>O'Brien, Nathan J. ; Amran, Syazwani ; Medan, Jelena ; Cleary, Ben ; Deady, Leslie W. ; Jennings, Ian G. ; Thompson, Philip E. ; Abbott, Belinda M.</creatorcontrib><description>Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl‐substituted analogues were further derivatized as prodrugs resulting in restoration of cell‐based activity. These data provide a conceptual model for development of tumor‐targeting prodrug forms of cell‐impermeable PI3K inhibitors.</description><identifier>ISSN: 1860-7179</identifier><identifier>EISSN: 1860-7187</identifier><identifier>DOI: 10.1002/cmdc.201200583</identifier><identifier>PMID: 23568455</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Cell Proliferation - drug effects ; Chromones - chemical synthesis ; Chromones - chemistry ; Chromones - pharmacology ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Humans ; inhibitors ; LY294002 ; MCF-7 Cells ; Molecular Structure ; Morpholines - chemical synthesis ; Morpholines - chemistry ; Morpholines - pharmacology ; phosphatidylinositol 3-kinase ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; PI3K ; prodrugs ; Prodrugs - chemical synthesis ; Prodrugs - chemistry ; Prodrugs - pharmacology ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Structure-Activity Relationship ; tetrazoles</subject><ispartof>ChemMedChem, 2013-06, Vol.8 (6), p.914-918</ispartof><rights>Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2283-61ecd7e1d463b84840882aa22771de42c6800ed26d446d4b3fadd75b909710b43</citedby><cites>FETCH-LOGICAL-c2283-61ecd7e1d463b84840882aa22771de42c6800ed26d446d4b3fadd75b909710b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcmdc.201200583$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcmdc.201200583$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23568455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'Brien, Nathan J.</creatorcontrib><creatorcontrib>Amran, Syazwani</creatorcontrib><creatorcontrib>Medan, Jelena</creatorcontrib><creatorcontrib>Cleary, Ben</creatorcontrib><creatorcontrib>Deady, Leslie W.</creatorcontrib><creatorcontrib>Jennings, Ian G.</creatorcontrib><creatorcontrib>Thompson, Philip E.</creatorcontrib><creatorcontrib>Abbott, Belinda M.</creatorcontrib><title>Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms</title><title>ChemMedChem</title><addtitle>ChemMedChem</addtitle><description>Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl‐substituted analogues were further derivatized as prodrugs resulting in restoration of cell‐based activity. These data provide a conceptual model for development of tumor‐targeting prodrug forms of cell‐impermeable PI3K inhibitors.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Proliferation - drug effects</subject><subject>Chromones - chemical synthesis</subject><subject>Chromones - chemistry</subject><subject>Chromones - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Humans</subject><subject>inhibitors</subject><subject>LY294002</subject><subject>MCF-7 Cells</subject><subject>Molecular Structure</subject><subject>Morpholines - chemical synthesis</subject><subject>Morpholines - chemistry</subject><subject>Morpholines - pharmacology</subject><subject>phosphatidylinositol 3-kinase</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>PI3K</subject><subject>prodrugs</subject><subject>Prodrugs - chemical synthesis</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - pharmacology</subject><subject>Protein Kinase Inhibitors - chemical synthesis</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>tetrazoles</subject><issn>1860-7179</issn><issn>1860-7187</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9v1DAQxS1ERUvhyhH5WA7Z-l9i51ht6bJ0S_cA6tFy4gkxJPHWzgK5cYAvyiepV1tW3NBoNCPP7z1ZD6FXlMwoIey87m09Y4QyQnLFn6ATqgqSSark08Muy2P0PMYvhAihqHqGjhnPCyXy_AT9WvsRhhEvh9ZVbvQhYt_gdevjpjWjs1PnBh_Tofvz8zfHZ-slf4Ov3WAi4DERuDXfAF8Mo9sE37kGQlLtXuo03Djh26Gb8F0LA76ELl0CWGwiXgdvw_YzvvKhjy_QUWO6CC8f5yn6dPX24_xdtrpdLOcXq6xmTPGsoFBbCdSKgldKKEGUYsYwJiW1IFhdKELAssIKkbrijbFW5lVJSklJJfgpOtv7pr_ebyGOunexhq4zA_ht1DTFwosyVUJne7QOPsYAjd4E15swaUr0Lnm9S14fkk-C14_e26oHe8D_Rp2Acg98dx1M_7HT85vL-b_m2V7r4gg_DloTvupCcpnruw8Lnd8QsViV7_WCPwBgMaCO</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>O'Brien, Nathan J.</creator><creator>Amran, Syazwani</creator><creator>Medan, Jelena</creator><creator>Cleary, Ben</creator><creator>Deady, Leslie W.</creator><creator>Jennings, Ian G.</creator><creator>Thompson, Philip E.</creator><creator>Abbott, Belinda M.</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201306</creationdate><title>Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms</title><author>O'Brien, Nathan J. ; Amran, Syazwani ; Medan, Jelena ; Cleary, Ben ; Deady, Leslie W. ; Jennings, Ian G. ; Thompson, Philip E. ; Abbott, Belinda M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2283-61ecd7e1d463b84840882aa22771de42c6800ed26d446d4b3fadd75b909710b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Proliferation - drug effects</topic><topic>Chromones - chemical synthesis</topic><topic>Chromones - chemistry</topic><topic>Chromones - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Humans</topic><topic>inhibitors</topic><topic>LY294002</topic><topic>MCF-7 Cells</topic><topic>Molecular Structure</topic><topic>Morpholines - chemical synthesis</topic><topic>Morpholines - chemistry</topic><topic>Morpholines - pharmacology</topic><topic>phosphatidylinositol 3-kinase</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>PI3K</topic><topic>prodrugs</topic><topic>Prodrugs - chemical synthesis</topic><topic>Prodrugs - chemistry</topic><topic>Prodrugs - pharmacology</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>tetrazoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'Brien, Nathan J.</creatorcontrib><creatorcontrib>Amran, Syazwani</creatorcontrib><creatorcontrib>Medan, Jelena</creatorcontrib><creatorcontrib>Cleary, Ben</creatorcontrib><creatorcontrib>Deady, Leslie W.</creatorcontrib><creatorcontrib>Jennings, Ian G.</creatorcontrib><creatorcontrib>Thompson, Philip E.</creatorcontrib><creatorcontrib>Abbott, Belinda M.</creatorcontrib><collection>Istex</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><jtitle>ChemMedChem</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'Brien, Nathan J.</au><au>Amran, Syazwani</au><au>Medan, Jelena</au><au>Cleary, Ben</au><au>Deady, Leslie W.</au><au>Jennings, Ian G.</au><au>Thompson, Philip E.</au><au>Abbott, Belinda M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms</atitle><jtitle>ChemMedChem</jtitle><addtitle>ChemMedChem</addtitle><date>2013-06</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>914</spage><epage>918</epage><pages>914-918</pages><issn>1860-7179</issn><eissn>1860-7187</eissn><abstract>Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl‐substituted analogues were further derivatized as prodrugs resulting in restoration of cell‐based activity. These data provide a conceptual model for development of tumor‐targeting prodrug forms of cell‐impermeable PI3K inhibitors.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>23568455</pmid><doi>10.1002/cmdc.201200583</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1860-7179 |
| ispartof | ChemMedChem, 2013-06, Vol.8 (6), p.914-918 |
| issn | 1860-7179 1860-7187 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1356369696 |
| source | MEDLINE; Access via Wiley Online Library |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Proliferation - drug effects Chromones - chemical synthesis Chromones - chemistry Chromones - pharmacology Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Humans inhibitors LY294002 MCF-7 Cells Molecular Structure Morpholines - chemical synthesis Morpholines - chemistry Morpholines - pharmacology phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism PI3K prodrugs Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - pharmacology Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Structure-Activity Relationship tetrazoles |
| title | Potent Inhibitors of Phosphatidylinositol 3 (PI3) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T08%3A04%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Potent%20Inhibitors%20of%20Phosphatidylinositol%E2%80%853%20(PI3)%20Kinase%20that%20have%20Antiproliferative%20Activity%20Only%20When%20Delivered%20as%20Prodrug%20Forms&rft.jtitle=ChemMedChem&rft.au=O'Brien,%20Nathan%20J.&rft.date=2013-06&rft.volume=8&rft.issue=6&rft.spage=914&rft.epage=918&rft.pages=914-918&rft.issn=1860-7179&rft.eissn=1860-7187&rft_id=info:doi/10.1002/cmdc.201200583&rft_dat=%3Cproquest_cross%3E1356369696%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1356369696&rft_id=info:pmid/23568455&rfr_iscdi=true |