Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors
[Display omitted] Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2021-10, Vol.50, p.128352-128352, Article 128352 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 128352 |
|---|---|
| container_issue | |
| container_start_page | 128352 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 50 |
| creator | Xiao, Yufang Huck, Bayard R. Lan, Ruoxi DeSelm, Lizbeth Chen, Xiaoling Qiu, Hui Neagu, Constantin Johnson, Theresa Mochalkin, Igor Gardberg, Anna Jiang, Xuliang Tian, Hui Dutt, Vikram Santos, Dusica Head, Jared Jackson, Jennifer Syed, Sakeena Lin, Jing Wilker, Erik Ma, Jianguo Clark, Anderson Machl, Andreas Bankston, Donald Jones, Christopher C.V. Goutopoulos, Andreas Sherer, Brian |
| description | [Display omitted]
Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po. |
| doi_str_mv | 10.1016/j.bmcl.2021.128352 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2569614711</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X21005795</els_id><sourcerecordid>2569614711</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-71dff2aeabaa6ce1785135e49f619d109a385dabeb6ce16b40c742b699ad4d093</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EglL4ARbISzYpnsRxYokN4i2QQDwkdpZjT1qXJC52itS_J1WBJatZzLlXuoeQI2ATYCBO55OqNc0kZSlMIC2zPN0iI-CCJxln-TYZMSlYUkr-vkf2Y5wzBpxxvkv2Ms5LkGUxIs-XLhr_hWFFfU15olvX-cUquNZZ1yHVnW78NFId6cxNZ82KLnyPXU_tUjf0qWAv4v70_KOnrpu5yvU-xAOyU-sm4uHPHZO366vXi9vk4fHm7uL8ITFZLvqkAFvXqUZdaS0MQlHmkOXIZS1AWmBSZ2VudYXV-isqzkzB00pIqS23TGZjcrLpXQT_ucTYq3bYgk2jO_TLqNJcSAG8ABjQdIOa4GMMWKvFsFCHlQKm1i7VXK1dqrVLtXE5hI5_-pdVi_Yv8itvAM42AA4rvxwGFY3DzqB1AU2vrHf_9X8DpaaFLA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2569614711</pqid></control><display><type>article</type><title>Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Xiao, Yufang ; Huck, Bayard R. ; Lan, Ruoxi ; DeSelm, Lizbeth ; Chen, Xiaoling ; Qiu, Hui ; Neagu, Constantin ; Johnson, Theresa ; Mochalkin, Igor ; Gardberg, Anna ; Jiang, Xuliang ; Tian, Hui ; Dutt, Vikram ; Santos, Dusica ; Head, Jared ; Jackson, Jennifer ; Syed, Sakeena ; Lin, Jing ; Wilker, Erik ; Ma, Jianguo ; Clark, Anderson ; Machl, Andreas ; Bankston, Donald ; Jones, Christopher C.V. ; Goutopoulos, Andreas ; Sherer, Brian</creator><creatorcontrib>Xiao, Yufang ; Huck, Bayard R. ; Lan, Ruoxi ; DeSelm, Lizbeth ; Chen, Xiaoling ; Qiu, Hui ; Neagu, Constantin ; Johnson, Theresa ; Mochalkin, Igor ; Gardberg, Anna ; Jiang, Xuliang ; Tian, Hui ; Dutt, Vikram ; Santos, Dusica ; Head, Jared ; Jackson, Jennifer ; Syed, Sakeena ; Lin, Jing ; Wilker, Erik ; Ma, Jianguo ; Clark, Anderson ; Machl, Andreas ; Bankston, Donald ; Jones, Christopher C.V. ; Goutopoulos, Andreas ; Sherer, Brian</creatorcontrib><description>[Display omitted]
Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2021.128352</identifier><identifier>PMID: 34481987</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>4-Aminopyrimidines ; Akt ; Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Area Under Curve ; Breast cancer ; Dogs ; Drug Discovery ; Female ; Half-Life ; Haplorhini ; Mammary Neoplasms, Animal - drug therapy ; Mice ; Molecular Docking Simulation ; Molecular Structure ; p70S6K ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Pyrimidines - chemistry ; Pyrimidines - pharmacokinetics ; Pyrimidines - pharmacology ; Rats ; Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors ; Ribosomal Protein S6 Kinases, 70-kDa - genetics ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Structure-Activity Relationship ; TOR Serine-Threonine Kinases - genetics ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2021-10, Vol.50, p.128352-128352, Article 128352</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-71dff2aeabaa6ce1785135e49f619d109a385dabeb6ce16b40c742b699ad4d093</citedby><cites>FETCH-LOGICAL-c356t-71dff2aeabaa6ce1785135e49f619d109a385dabeb6ce16b40c742b699ad4d093</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.2021.128352$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34481987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Yufang</creatorcontrib><creatorcontrib>Huck, Bayard R.</creatorcontrib><creatorcontrib>Lan, Ruoxi</creatorcontrib><creatorcontrib>DeSelm, Lizbeth</creatorcontrib><creatorcontrib>Chen, Xiaoling</creatorcontrib><creatorcontrib>Qiu, Hui</creatorcontrib><creatorcontrib>Neagu, Constantin</creatorcontrib><creatorcontrib>Johnson, Theresa</creatorcontrib><creatorcontrib>Mochalkin, Igor</creatorcontrib><creatorcontrib>Gardberg, Anna</creatorcontrib><creatorcontrib>Jiang, Xuliang</creatorcontrib><creatorcontrib>Tian, Hui</creatorcontrib><creatorcontrib>Dutt, Vikram</creatorcontrib><creatorcontrib>Santos, Dusica</creatorcontrib><creatorcontrib>Head, Jared</creatorcontrib><creatorcontrib>Jackson, Jennifer</creatorcontrib><creatorcontrib>Syed, Sakeena</creatorcontrib><creatorcontrib>Lin, Jing</creatorcontrib><creatorcontrib>Wilker, Erik</creatorcontrib><creatorcontrib>Ma, Jianguo</creatorcontrib><creatorcontrib>Clark, Anderson</creatorcontrib><creatorcontrib>Machl, Andreas</creatorcontrib><creatorcontrib>Bankston, Donald</creatorcontrib><creatorcontrib>Jones, Christopher C.V.</creatorcontrib><creatorcontrib>Goutopoulos, Andreas</creatorcontrib><creatorcontrib>Sherer, Brian</creatorcontrib><title>Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po.</description><subject>4-Aminopyrimidines</subject><subject>Akt</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Area Under Curve</subject><subject>Breast cancer</subject><subject>Dogs</subject><subject>Drug Discovery</subject><subject>Female</subject><subject>Half-Life</subject><subject>Haplorhini</subject><subject>Mammary Neoplasms, Animal - drug therapy</subject><subject>Mice</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Structure</subject><subject>p70S6K</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - pharmacokinetics</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - genetics</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EglL4ARbISzYpnsRxYokN4i2QQDwkdpZjT1qXJC52itS_J1WBJatZzLlXuoeQI2ATYCBO55OqNc0kZSlMIC2zPN0iI-CCJxln-TYZMSlYUkr-vkf2Y5wzBpxxvkv2Ms5LkGUxIs-XLhr_hWFFfU15olvX-cUquNZZ1yHVnW78NFId6cxNZ82KLnyPXU_tUjf0qWAv4v70_KOnrpu5yvU-xAOyU-sm4uHPHZO366vXi9vk4fHm7uL8ITFZLvqkAFvXqUZdaS0MQlHmkOXIZS1AWmBSZ2VudYXV-isqzkzB00pIqS23TGZjcrLpXQT_ucTYq3bYgk2jO_TLqNJcSAG8ABjQdIOa4GMMWKvFsFCHlQKm1i7VXK1dqrVLtXE5hI5_-pdVi_Yv8itvAM42AA4rvxwGFY3DzqB1AU2vrHf_9X8DpaaFLA</recordid><startdate>20211015</startdate><enddate>20211015</enddate><creator>Xiao, Yufang</creator><creator>Huck, Bayard R.</creator><creator>Lan, Ruoxi</creator><creator>DeSelm, Lizbeth</creator><creator>Chen, Xiaoling</creator><creator>Qiu, Hui</creator><creator>Neagu, Constantin</creator><creator>Johnson, Theresa</creator><creator>Mochalkin, Igor</creator><creator>Gardberg, Anna</creator><creator>Jiang, Xuliang</creator><creator>Tian, Hui</creator><creator>Dutt, Vikram</creator><creator>Santos, Dusica</creator><creator>Head, Jared</creator><creator>Jackson, Jennifer</creator><creator>Syed, Sakeena</creator><creator>Lin, Jing</creator><creator>Wilker, Erik</creator><creator>Ma, Jianguo</creator><creator>Clark, Anderson</creator><creator>Machl, Andreas</creator><creator>Bankston, Donald</creator><creator>Jones, Christopher C.V.</creator><creator>Goutopoulos, Andreas</creator><creator>Sherer, Brian</creator><general>Elsevier Ltd</general><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>20211015</creationdate><title>Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors</title><author>Xiao, Yufang ; Huck, Bayard R. ; Lan, Ruoxi ; DeSelm, Lizbeth ; Chen, Xiaoling ; Qiu, Hui ; Neagu, Constantin ; Johnson, Theresa ; Mochalkin, Igor ; Gardberg, Anna ; Jiang, Xuliang ; Tian, Hui ; Dutt, Vikram ; Santos, Dusica ; Head, Jared ; Jackson, Jennifer ; Syed, Sakeena ; Lin, Jing ; Wilker, Erik ; Ma, Jianguo ; Clark, Anderson ; Machl, Andreas ; Bankston, Donald ; Jones, Christopher C.V. ; Goutopoulos, Andreas ; Sherer, Brian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-71dff2aeabaa6ce1785135e49f619d109a385dabeb6ce16b40c742b699ad4d093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>4-Aminopyrimidines</topic><topic>Akt</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Area Under Curve</topic><topic>Breast cancer</topic><topic>Dogs</topic><topic>Drug Discovery</topic><topic>Female</topic><topic>Half-Life</topic><topic>Haplorhini</topic><topic>Mammary Neoplasms, Animal - drug therapy</topic><topic>Mice</topic><topic>Molecular Docking Simulation</topic><topic>Molecular Structure</topic><topic>p70S6K</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacokinetics</topic><topic>Pyrimidines - pharmacology</topic><topic>Rats</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - genetics</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Yufang</creatorcontrib><creatorcontrib>Huck, Bayard R.</creatorcontrib><creatorcontrib>Lan, Ruoxi</creatorcontrib><creatorcontrib>DeSelm, Lizbeth</creatorcontrib><creatorcontrib>Chen, Xiaoling</creatorcontrib><creatorcontrib>Qiu, Hui</creatorcontrib><creatorcontrib>Neagu, Constantin</creatorcontrib><creatorcontrib>Johnson, Theresa</creatorcontrib><creatorcontrib>Mochalkin, Igor</creatorcontrib><creatorcontrib>Gardberg, Anna</creatorcontrib><creatorcontrib>Jiang, Xuliang</creatorcontrib><creatorcontrib>Tian, Hui</creatorcontrib><creatorcontrib>Dutt, Vikram</creatorcontrib><creatorcontrib>Santos, Dusica</creatorcontrib><creatorcontrib>Head, Jared</creatorcontrib><creatorcontrib>Jackson, Jennifer</creatorcontrib><creatorcontrib>Syed, Sakeena</creatorcontrib><creatorcontrib>Lin, Jing</creatorcontrib><creatorcontrib>Wilker, Erik</creatorcontrib><creatorcontrib>Ma, Jianguo</creatorcontrib><creatorcontrib>Clark, Anderson</creatorcontrib><creatorcontrib>Machl, Andreas</creatorcontrib><creatorcontrib>Bankston, Donald</creatorcontrib><creatorcontrib>Jones, Christopher C.V.</creatorcontrib><creatorcontrib>Goutopoulos, Andreas</creatorcontrib><creatorcontrib>Sherer, Brian</creatorcontrib><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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Yufang</au><au>Huck, Bayard R.</au><au>Lan, Ruoxi</au><au>DeSelm, Lizbeth</au><au>Chen, Xiaoling</au><au>Qiu, Hui</au><au>Neagu, Constantin</au><au>Johnson, Theresa</au><au>Mochalkin, Igor</au><au>Gardberg, Anna</au><au>Jiang, Xuliang</au><au>Tian, Hui</au><au>Dutt, Vikram</au><au>Santos, Dusica</au><au>Head, Jared</au><au>Jackson, Jennifer</au><au>Syed, Sakeena</au><au>Lin, Jing</au><au>Wilker, Erik</au><au>Ma, Jianguo</au><au>Clark, Anderson</au><au>Machl, Andreas</au><au>Bankston, Donald</au><au>Jones, Christopher C.V.</au><au>Goutopoulos, Andreas</au><au>Sherer, Brian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2021-10-15</date><risdate>2021</risdate><volume>50</volume><spage>128352</spage><epage>128352</epage><pages>128352-128352</pages><artnum>128352</artnum><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays. SAR optimization improved Akt enzymatic and p70S6K cellular potencies, reduced hERG liability, and ultimately discovered the promising candidate 37, which exhibited with a single digit nanomolar value in both p70S6K and Akt biochemical assays, and hERG activities (IC50 = 17.4 μM). This agent demonstrated dose-dependent efficacy in inhibiting mice breast cancer tumor growth and covered more than 90% pS6 inhibition up to 24 h at a dose of 200 mg/kg po.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34481987</pmid><doi>10.1016/j.bmcl.2021.128352</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2021-10, Vol.50, p.128352-128352, Article 128352 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2569614711 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | 4-Aminopyrimidines Akt Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Area Under Curve Breast cancer Dogs Drug Discovery Female Half-Life Haplorhini Mammary Neoplasms, Animal - drug therapy Mice Molecular Docking Simulation Molecular Structure p70S6K Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Pyrimidines - chemistry Pyrimidines - pharmacokinetics Pyrimidines - pharmacology Rats Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors Ribosomal Protein S6 Kinases, 70-kDa - genetics Ribosomal Protein S6 Kinases, 70-kDa - metabolism Structure-Activity Relationship TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism |
| title | Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T05%3A48%3A54IST&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=Discovery%20of%204-aminopyrimidine%20analogs%20as%20highly%20potent%20dual%20P70S6K/Akt%20inhibitors&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Xiao,%20Yufang&rft.date=2021-10-15&rft.volume=50&rft.spage=128352&rft.epage=128352&rft.pages=128352-128352&rft.artnum=128352&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2021.128352&rft_dat=%3Cproquest_cross%3E2569614711%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=2569614711&rft_id=info:pmid/34481987&rft_els_id=S0960894X21005795&rfr_iscdi=true |