Expert
Reviews in Molecular Medicine: http://www.expertreviews.org/
DOI: 10.1017/S1462399408000641; 19 March 2008
Alex
W. White, Andrew D. Westwell and Ghali Brahemi (2008) Protein–protein interactions
as targets for small-molecule therapeutics in cancer. Expert Rev. Mol. Med.
Vol. 10, e8, DOI: 10.1017/S1462399408000641
Protein–protein
interactions as targets for small-molecule therapeutics in cancer
Alex W. White a1
c1 , Andrew D. Westwell a1 and Ghali Brahemi a1
a1 Welsh School
of Pharmacy, King Edward VII Avenue, Cardiff University, Cardiff, CF10 3NB,
UK.
c1 Corresponding
author: Alex W. White, Welsh School of Pharmacy, King Edward VII Avenue, Cardiff
University, Cardiff, CF10 3NB, UK. Tel: +44 (0)29 2087 6308; Fax: +44 (0)29
2087 4149; E-mail: whiteaw@cf.ac.uk
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.
Full
text online (purchase or subscribe through
Cambridge Journals Online)
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