Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Kinase inhibitors

Analysing kinase inhibitor selectivity

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.

ORIGINAL RESEARCH PAPERS

  1. 1

    Anastassiadis, T. et al. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nature Biotech. 29, 1039–1045 (2011)

    CAS  Article  Google Scholar 

  2. 2

    Davis, M. I. et al. Comprehensive analysis of kinase inhibitor selectivity. Nature Biotech. 29, 1046–1051 (2011

    CAS  Article  Google Scholar 

Download references

Authors

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

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing