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. Structure-activity relationship (SAR) analysis is used for guidance of the design of potent and selective compounds. Additional properties of the lead compounds, such as safety and selectivity, metabolic stability and other pharmacokinetic properties (referred to as ADMET), are also assessed and optimized at this stage.
CETSA® data can be used to correlate target engagement in the cell with functional readouts and to establish a SAR. This will ensure that your project stays on track and that you are prioritizing only the very best compounds at each stage.
A cellular target engagement assay that determines the level of interaction between a compound and the target protein in a physiologically relevant setting is pivotal to understand which compounds to prioritize for further optimization. Therefore, including CETSA® in the screening cascade in lead optimization is important to ensure a relevant compound design and thereby enhance the lead optimization. Lead optimization can be extremely time-consuming and costly, so tools such as CETSA® that help you to speed up timelines and minimize delays are very valuable during this stage of drug discovery.