Cited by 1,137Computational Drug Discovery MethodsChemical Synthesis and AnalysisProtein Degradation and Inhibitors

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Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

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Scott, Duncan E., Bayly, Andrew R., Abell, Chris, Skidmore, John·2016·Nature Reviews Drug Discovery

DOI 10.1038/nrd.2016.29

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Abstract

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.

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Authors: Scott, D. E., Bayly, A. R., Abell, C., & Skidmore, J.
Affiliations: University of Cambridge (GB)
Corresponding author: Abell, Chris
Skidmore, John
ORCID: Scott, Duncan E.
Bayly, Andrew R.
Abell, Chris
Skidmore, John
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2016-04-11
Volume: 15
Issue: 8
Pages: 533-550
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd.2016.29
OpenAlex: W2329592726
Cited by: 1,137
References: 172
Citations by year: 2026: 101 · 2025: 121 · 2024: 120 · 2023: 115 · 2022: 117 · 2021: 128 · 2020: 120 · 2019: 106 · 2018: 107 · 2017: 83 · 2016: 16
FWCI: 8.11
Type: journal article
Language: en
Open access: green
www.repository.cam.ac.uk
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Apollo (University of Cambridge) (submittedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords: protein-protein interaction, PPI inhibitors, small molecule drug discovery, drug target identification, structure-based drug design
MeSH terms: Animals, Humans, Models, Molecular, Proteins, Protein Structure, Tertiary, Computational Biology, Protein Interaction Domains and Motifs, Small Molecule Libraries, Drug Discovery

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Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

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