Reaching for high-hanging fruit in drug discovery at protein–protein interfaces View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-12-12

AUTHORS

James A. Wells, Christopher L. McClendon

ABSTRACT

Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-molecule drugs that disrupt protein–protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein–protein interfaces might be more tractable than has been thought. These studies discovered small molecules that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein–protein interactions. Remarkably, these small molecules bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach. More... »

PAGES

1001-1009

Journal

TITLE

Nature

ISSUE

7172

VOLUME

450

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature06526

    DOI

    http://dx.doi.org/10.1038/nature06526

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1038231590

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18075579


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