Target Engagement Assays in Early Drug Discovery.
Loading...
Embargo End Date
ICR Authors
Authors
St John-Campbell, S
Bhalay, G
Bhalay, G
Document Type
Journal Article
Date
2025-06-26
Date Accepted
2025-05-14
Abstract
In target-based drug discovery, quantification of target engagement is required to build structure-activity relationships and develop a potent clinical candidate. Target engagement data also provides evidence of a drug's mechanism of action (MoA) which although is not required for approval, can increase the chance of a successful clinical outcome. Consequently, a plethora of assays has been developed to provide information about target engagement on isolated proteins and in cells. These techniques monitor changes in stability, structure, optical properties or mass difference between proteins and their complexes with ligands. They also provide characterization of the compound with thermodynamic, kinetic and structural binding parameters. The diversity of approaches reflects the challenges faced when drugging different protein classes, with each method having advantages, trade-offs and target specificity.
Citation
Journal of Medicinal Chemistry, 2025, 68 (12), pp. 12331 - 12368
Source Title
Journal of Medicinal Chemistry
Publisher
AMER CHEMICAL SOC
ISSN
0022-2623
eISSN
1520-4804
Collections
Research Team
Medicinal Chemistry 1