Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Scott, Duncan E
Bayly, Andrew R
Abell, Chris https://orcid.org/0000-0001-9174-1987
Skidmore, John https://orcid.org/0000-0001-9108-7858
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.
Description
Keywords
Animals, Computational Biology, Drug Discovery, Humans, Models, Molecular, Protein Interaction Domains and Motifs, Protein Structure, Tertiary, Proteins, Small Molecule Libraries
Journal Title
Nat Rev Drug Discov
Conference Name
Journal ISSN
1474-1776
1474-1784
1474-1784
Volume Title
15
Publisher
Springer Science and Business Media LLC
Publisher DOI
Sponsorship
JS, DES and ARB thank the Wellcome Trust for funding.