Cited by 122Chemical Synthesis and AnalysisComputational Drug Discovery MethodsProtein Degradation and Inhibitors

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

White, Alex W., Westwell, Andrew D., Brahemi, Ghali·2008·Expert Reviews in Molecular Medicine

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.

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Crossref · 10.1017/s1462399408000641

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Authors
White, A. W., Westwell, A. D., & Brahemi, G.
Affiliations
Cardiff University (GB)
Corresponding author
White, Alex W.
Venue
Expert Reviews in Molecular Medicine
Published
2008-03
Volume
10
Pages
e8-e8
ISSN
1462-3994 (ISSN-L)
OpenAlex
W2161203845
Cited by
122
References
99
Citations by year
2026: 3 · 2025: 14 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 9 · 2012: 7
FWCI
0.57
Type
journal article
Language
en
Open access
closed
Locations
  • Expert Reviews in Molecular Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
protein-protein interaction, small molecule inhibitors, cancer therapeutics, drug design, protein-protein interfaces, hot spots
MeSH terms
Animals, Antineoplastic Agents, Binding Sites, Enzyme Inhibitors, Humans, Ligands, Neoplasms, Protein Binding, Proteins, Surface Properties, Biomarkers, Tumor, Drug Design, Signal Transduction

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