Including CETSA® in your assay cascade and using the EC50 data for potency ranking within your chemical series facilitates a relevant compound design yielding compounds with higher chance of therapeutic effect.
In drug discovery, selective binding of the compound to the right target is important for the drug to be both effective and safe. To achieve this, the drug must be present at the site of action and occupy the intended target with high specificity.
Targeted protein degradation is a novel modality with the potential to tackle therapeutically interesting proteins beyond the limitations of current existing approaches. In this area, CETSA® is a powerful technology which can be applied for investigating the degradation target
For a drug to be effective according to the target hypothesis, it must selectively bind to the intended target protein to elicit its effect. Target engagement (TE) is defined as the interaction of ligands with their molecular targets. Assessment of a compound’s TE is essential in the discovery and development of new therapies.
CETSA® can determine cellular target engagement in physiologically relevant settings of the native, full-length protein and can potentially unlock novel chemical space. CETSA® library screening in intact cells gives direct confirmation on target engagement of your library compounds in physiological conditions from the onset.
As a cellular target engagement assay that determines the level of interaction between a ligand and a target protein of interest in a physiologically relevant setting, CETSA® is perfectly suited for hit confirmation.
CETSA® can assess target engagement across a multitude of sample types. Established assays can easily be transferred from cell line to animal tissue, human primary cells, or patient-derived material, and thereby be used for translation all the way from lab bench to patient.
Since the protein targets of any given compound hit from a phenotypic screen are initially unknown, one major challenge with phenotypic-based drug discovery is the need for target identification or deconvolution.
Biomarkers are important to facilitate translation, validate the therapeutic hypothesis and monitor therapeutic effect in clinical trials and beyond. The identification of biomarkers is a time-demanding but crucial part of the preclinical drug discovery process
The aim at this stage of the drug discovery and development process is to optimize the compound properties to ensure the development of safe and effective candidate drugs (CDs) that can be dosed in healthy volunteers.