Structural biology contributions to tyrosine kinase drug discovery
Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provi...
Gespeichert in:
Veröffentlicht in: | Current opinion in cell biology 2009-04, Vol.21 (2), p.280-287 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 287 |
---|---|
container_issue | 2 |
container_start_page | 280 |
container_title | Current opinion in cell biology |
container_volume | 21 |
creator | Cowan-Jacob, Sandra W Möbitz, Henrik Fabbro, Doriano |
description | Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. Important progress has been made recently, both in academia and in the pharmaceutical industry, with respect to solving structures of inactive, multidomain or protein–protein complexes of kinases, which helps our understanding of the dynamics of regulation of kinase activity. This leads to a better understanding of how mutations lead to activation of kinases and resistance, in addition to providing opportunities for novel modes of targeting kinases. |
doi_str_mv | 10.1016/j.ceb.2009.01.012 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67128222</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0955067409000234</els_id><sourcerecordid>67128222</sourcerecordid><originalsourceid>FETCH-LOGICAL-c472t-11cfbcce4e0d5e79d78d3bb40da47b81d6d8e7cde1df9fa1f42f060849bcb3e93</originalsourceid><addsrcrecordid>eNp9kU9r3DAUxEVoSDZpPkAuxafevHlP1toWhUIb8g8COSQ9C0t6Dtp4rVSSA_72ldmFQg-FB7rMDKPfMHaJsEbA-mq7NqTXHECuAfPxI7bCtpElCIRPbAVysymhbsQpO4txCwA1cHnCTlFyaEXNV-zncwqTSVPohkI7P_jXuTB-TMHpKTk_xiL5Is3BRzdS8ebGLlJhw_RaWBeN_6Awf2bHfTdEuji85-zX7c3L9X35-HT3cP3jsTSi4alENL02hgSB3VAjbdPaSmsBthONbtHWtqXGWELby77DXvA-922F1EZXJKtz9nWf-x7874liUrtcgYahG8lPUdUN8pZznoW4F5pcOwbq1Xtwuy7MCkEt4NRWZXBqAacA8y2eL4fwSe_I_nUcSGXBt72A8hc_HAUVjaPRkHWBTFLWu__Gf__HbQY3OtMNbzRT3PopjJmdQhW5AvW8LLcMBzKPxitR_QGhG5Tb</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67128222</pqid></control><display><type>article</type><title>Structural biology contributions to tyrosine kinase drug discovery</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Cowan-Jacob, Sandra W ; Möbitz, Henrik ; Fabbro, Doriano</creator><creatorcontrib>Cowan-Jacob, Sandra W ; Möbitz, Henrik ; Fabbro, Doriano</creatorcontrib><description>Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. Important progress has been made recently, both in academia and in the pharmaceutical industry, with respect to solving structures of inactive, multidomain or protein–protein complexes of kinases, which helps our understanding of the dynamics of regulation of kinase activity. This leads to a better understanding of how mutations lead to activation of kinases and resistance, in addition to providing opportunities for novel modes of targeting kinases.</description><identifier>ISSN: 0955-0674</identifier><identifier>EISSN: 1879-0410</identifier><identifier>DOI: 10.1016/j.ceb.2009.01.012</identifier><identifier>PMID: 19208462</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Binding Sites ; Drug Design ; Drug Discovery ; Humans ; Internal Medicine ; Molecular Structure ; Mutation ; Neoplasms - drug therapy ; Protein Conformation ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - therapeutic use ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - chemistry ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Structure-Activity Relationship ; Substrate Specificity</subject><ispartof>Current opinion in cell biology, 2009-04, Vol.21 (2), p.280-287</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-11cfbcce4e0d5e79d78d3bb40da47b81d6d8e7cde1df9fa1f42f060849bcb3e93</citedby><cites>FETCH-LOGICAL-c472t-11cfbcce4e0d5e79d78d3bb40da47b81d6d8e7cde1df9fa1f42f060849bcb3e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ceb.2009.01.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19208462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cowan-Jacob, Sandra W</creatorcontrib><creatorcontrib>Möbitz, Henrik</creatorcontrib><creatorcontrib>Fabbro, Doriano</creatorcontrib><title>Structural biology contributions to tyrosine kinase drug discovery</title><title>Current opinion in cell biology</title><addtitle>Curr Opin Cell Biol</addtitle><description>Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. Important progress has been made recently, both in academia and in the pharmaceutical industry, with respect to solving structures of inactive, multidomain or protein–protein complexes of kinases, which helps our understanding of the dynamics of regulation of kinase activity. This leads to a better understanding of how mutations lead to activation of kinases and resistance, in addition to providing opportunities for novel modes of targeting kinases.</description><subject>Binding Sites</subject><subject>Drug Design</subject><subject>Drug Discovery</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Molecular Structure</subject><subject>Mutation</subject><subject>Neoplasms - drug therapy</subject><subject>Protein Conformation</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Protein-Tyrosine Kinases - chemistry</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Substrate Specificity</subject><issn>0955-0674</issn><issn>1879-0410</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9r3DAUxEVoSDZpPkAuxafevHlP1toWhUIb8g8COSQ9C0t6Dtp4rVSSA_72ldmFQg-FB7rMDKPfMHaJsEbA-mq7NqTXHECuAfPxI7bCtpElCIRPbAVysymhbsQpO4txCwA1cHnCTlFyaEXNV-zncwqTSVPohkI7P_jXuTB-TMHpKTk_xiL5Is3BRzdS8ebGLlJhw_RaWBeN_6Awf2bHfTdEuji85-zX7c3L9X35-HT3cP3jsTSi4alENL02hgSB3VAjbdPaSmsBthONbtHWtqXGWELby77DXvA-922F1EZXJKtz9nWf-x7874liUrtcgYahG8lPUdUN8pZznoW4F5pcOwbq1Xtwuy7MCkEt4NRWZXBqAacA8y2eL4fwSe_I_nUcSGXBt72A8hc_HAUVjaPRkHWBTFLWu__Gf__HbQY3OtMNbzRT3PopjJmdQhW5AvW8LLcMBzKPxitR_QGhG5Tb</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Cowan-Jacob, Sandra W</creator><creator>Möbitz, Henrik</creator><creator>Fabbro, Doriano</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>20090401</creationdate><title>Structural biology contributions to tyrosine kinase drug discovery</title><author>Cowan-Jacob, Sandra W ; Möbitz, Henrik ; Fabbro, Doriano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-11cfbcce4e0d5e79d78d3bb40da47b81d6d8e7cde1df9fa1f42f060849bcb3e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Binding Sites</topic><topic>Drug Design</topic><topic>Drug Discovery</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Molecular Structure</topic><topic>Mutation</topic><topic>Neoplasms - drug therapy</topic><topic>Protein Conformation</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Protein-Tyrosine Kinases - chemistry</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cowan-Jacob, Sandra W</creatorcontrib><creatorcontrib>Möbitz, Henrik</creatorcontrib><creatorcontrib>Fabbro, Doriano</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>Current opinion in cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cowan-Jacob, Sandra W</au><au>Möbitz, Henrik</au><au>Fabbro, Doriano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural biology contributions to tyrosine kinase drug discovery</atitle><jtitle>Current opinion in cell biology</jtitle><addtitle>Curr Opin Cell Biol</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>21</volume><issue>2</issue><spage>280</spage><epage>287</epage><pages>280-287</pages><issn>0955-0674</issn><eissn>1879-0410</eissn><abstract>Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of kinases and in particular of tyrosine kinases has given detailed insights into the intrinsic flexibility of the catalytic domain and has provided a rational basis for obtaining selective inhibitors. Important progress has been made recently, both in academia and in the pharmaceutical industry, with respect to solving structures of inactive, multidomain or protein–protein complexes of kinases, which helps our understanding of the dynamics of regulation of kinase activity. This leads to a better understanding of how mutations lead to activation of kinases and resistance, in addition to providing opportunities for novel modes of targeting kinases.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19208462</pmid><doi>10.1016/j.ceb.2009.01.012</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0955-0674 |
ispartof | Current opinion in cell biology, 2009-04, Vol.21 (2), p.280-287 |
issn | 0955-0674 1879-0410 |
language | eng |
recordid | cdi_proquest_miscellaneous_67128222 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Binding Sites Drug Design Drug Discovery Humans Internal Medicine Molecular Structure Mutation Neoplasms - drug therapy Protein Conformation Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - therapeutic use Protein-Tyrosine Kinases - antagonists & inhibitors Protein-Tyrosine Kinases - chemistry Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Structure-Activity Relationship Substrate Specificity |
title | Structural biology contributions to tyrosine kinase drug discovery |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T01%3A53%3A28IST&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=Structural%20biology%20contributions%20to%20tyrosine%20kinase%20drug%20discovery&rft.jtitle=Current%20opinion%20in%20cell%20biology&rft.au=Cowan-Jacob,%20Sandra%20W&rft.date=2009-04-01&rft.volume=21&rft.issue=2&rft.spage=280&rft.epage=287&rft.pages=280-287&rft.issn=0955-0674&rft.eissn=1879-0410&rft_id=info:doi/10.1016/j.ceb.2009.01.012&rft_dat=%3Cproquest_cross%3E67128222%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=67128222&rft_id=info:pmid/19208462&rft_els_id=S0955067409000234&rfr_iscdi=true |