1. Importance of Quantifying Drug-Target Engagement in Cells
- Author
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Huber Kvm. and J Stefaniak
- Subjects
Drug ,010405 organic chemistry ,Chemistry ,media_common.quotation_subject ,Organic Chemistry ,Drug target ,Chemical biology ,Cellular homeostasis ,Computational biology ,01 natural sciences ,Biochemistry ,Receptor–ligand kinetics ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Therapeutic index ,Drug development ,Drug Discovery ,Intracellular ,media_common - Abstract
Measuring and quantifying the binding of a drug to a protein target inside living cells and thereby correlating biochemical or biophysical activity with target engagement in cells or tissue represents a key step in target validation and drug development. A prototypic target engagement assay should allow for unbiased determination of small molecule-protein interactions in order to confirm cellular mechanism-of-action (MoA) while avoiding major artificial perturbations of cellular homeostasis and integrity. Recently, several new additions to the chemical biology toolbox have expanded our ability to study drug action in intact cells and enabled surveying of intracellular residence time and binding kinetics, which are particularly important for potent receptor ligands and therapeutic moieties with limited therapeutic index.
- Published
- 2020