Analysing kinase inhibitor selectivity

Analysing kinase inhibitor selectivity

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Access through your institution Buy or subscribe Most small-molecule kinase inhibitors interact with multiple members of the protein kinase family; achieving selective inhibition of specific protein kinases is challenging. These two papers describe studies of kinase inhibitor selectivity. Anastassiadis _et al_. profiled the activity of 178 kinase inhibitors against a panel of 300 protein kinases. They identified kinases that were inhibited by many compounds, as well as kinases that were resistant to small-molecule inhibition, and showed that many off-target interactions occur with seemingly unrelated kinases. They also identified potential lead compounds for orphan kinases and for the development of multitargeted kinase inhibitors. Davis _et al_. tested the interaction of 72 kinase inhibitors with 442 kinases. They showed that, as a group, type II inhibitors — which bind adjacently to the ATP site and prefer an inactive kinase conformation — were generally more selective than type I inhibitors but several individual type I inhibitors were among the most selective identified. Furthermore, they identified a class of inhibitors that was broadly active against a single subfamily of kinases but selective outside that subfamily, and several compounds that were active against orphan kinases. Together, these papers provide information that could aid the identification of selective kinase inhibitors for use as tool compounds, and assist in kinase inhibitor drug discovery. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH PAPERS * Anastassiadis, T. et al. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. _Nature Biotech._ 29, 1039–1045 (2011) Article  CAS  Google Scholar  * Davis, M. I. et al. Comprehensive analysis of kinase inhibitor selectivity. _Nature Biotech._ 29, 1046–1051 (2011 Article  CAS  Google Scholar  Download references Authors * Charlotte Harrison View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Harrison, C. Analysing kinase inhibitor selectivity. _Nat Rev Drug Discov_ 11, 21 (2012). https://doi.org/10.1038/nrd3647 Download citation * Published: 03 January 2012 * Issue Date: January 2012 * DOI: https://doi.org/10.1038/nrd3647 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

Access through your institution Buy or subscribe Most small-molecule kinase inhibitors interact with multiple members of the protein kinase family; achieving selective inhibition of specific


protein kinases is challenging. These two papers describe studies of kinase inhibitor selectivity. Anastassiadis _et al_. profiled the activity of 178 kinase inhibitors against a panel of


300 protein kinases. They identified kinases that were inhibited by many compounds, as well as kinases that were resistant to small-molecule inhibition, and showed that many off-target


interactions occur with seemingly unrelated kinases. They also identified potential lead compounds for orphan kinases and for the development of multitargeted kinase inhibitors. Davis _et


al_. tested the interaction of 72 kinase inhibitors with 442 kinases. They showed that, as a group, type II inhibitors — which bind adjacently to the ATP site and prefer an inactive kinase


conformation — were generally more selective than type I inhibitors but several individual type I inhibitors were among the most selective identified. Furthermore, they identified a class of


inhibitors that was broadly active against a single subfamily of kinases but selective outside that subfamily, and several compounds that were active against orphan kinases. Together, these


papers provide information that could aid the identification of selective kinase inhibitors for use as tool compounds, and assist in kinase inhibitor drug discovery. This is a preview of


subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only


$17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout


ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH PAPERS * Anastassiadis, T. et al. Comprehensive


assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. _Nature Biotech._ 29, 1039–1045 (2011) Article  CAS  Google Scholar  * Davis, M. I. et al. Comprehensive


analysis of kinase inhibitor selectivity. _Nature Biotech._ 29, 1046–1051 (2011 Article  CAS  Google Scholar  Download references Authors * Charlotte Harrison View author publications You


can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Harrison, C. Analysing kinase inhibitor


selectivity. _Nat Rev Drug Discov_ 11, 21 (2012). https://doi.org/10.1038/nrd3647 Download citation * Published: 03 January 2012 * Issue Date: January 2012 * DOI:


https://doi.org/10.1038/nrd3647 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently


available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative