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Protein-protein interactions as targets for small-molecule therapeutics in cancer

White, Alex William, Westwell, Andrew and Brahemi, Ghali 2008. Protein-protein interactions as targets for small-molecule therapeutics in cancer. Expert Reviews in Molecular Medicine 10 (e8) , pp. 1-14. 10.1017/S1462399408000641

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Abstract

Small-molecule inhibition of the direct protein–protein interactions that mediate many important biological processes is an emerging and challenging area in drug design. Conventional drug design has mainly focused on the inhibition of a single protein, usually an enzyme or receptor, since these proteins often contain a clearly defined ligand-binding site with which a small-molecule drug can be designed to interact. Designing a small molecule to bind to a protein–protein interface and subsequently inhibit the interaction poses several challenges, including the initial identification of suitable protein–protein interactions, the surface area of the interface (it is often large), and the location of ‘hot spots’ (small regions suitable for drug binding). This article reviews the general approach to designing inhibitors of protein–protein interactions, and then focuses on recent advances in the use of small molecules targeted against a variety of protein–protein interactions that have therapeutic potential for cancer.

Item Type: Article
Status: Published
Schools: Pharmacy
Additional Information: Publisher’s copyright requirements: “All contributors retain the right to post the definitive version of the contribution as published at Cambridge Journals Online (in PDF or HTML form) in the Institutional Repository of the institution in which they worked at the time the paper was first submitted, or (for appropriate journals) in PubMed Central or UK PubMed Central, no sooner than one year after first publication of the paper in the journal, subject to file availability and provided the posting includes a prominent statement of the full bibliographical details, a copyright notice in the name of the copyright holder (Cambridge University Press or the sponsoring Society, as appropriate), and a link to the online edition of the journal at Cambridge Journals Online. Inclusion of this definitive version after one year in Institutional Repositories outside of the institution in which the contributor worked at the time the paper was first submitted will be subject to the additional permission of Cambridge University Press (not to be unreasonably withheld). See: http://journals.cambridge.org/action/forAuthors?page=copyright
Publisher: Cambridge University Press
ISSN: 1462-3994
Last Modified: 04 Jun 2017 01:58
URI: http://orca.cf.ac.uk/id/eprint/6769

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