Target Engagement

For a drug to be effective according to the target hypothesisit 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 therapiesTE assays enable direct comparisons of individual compounds’ affinity for their target(s) to be made. Because TE assays allow researchers to select compounds that have the best affinity for their intended target, and thus highest chance of relevant therapeutic effect, these are extremely useful to ensure the correct compound prioritization at each stage of the drug discovery process. In the absence of confirmation that a compound indeed interacts with the desired target, precious time can be lost and the chance of success decreases by the project moving in the wrong direction. 

CETSA® is well-suited for TE assessments and requires no protein or ligand modifications which makes the method faster and easier to set up compared to traditional assays. Moreover, CETSA® assesses the TE of compounds towards the endogenous target protein in a physiological relevant setting yielding a more therapeutically relevant measure compared to existing TE assays.  


Durham TB, Blanco MJ. Target engagement in lead generation. (2015) Bioorganic & medicinal chemistry letters. DOI: 10.1016/j.bmcl.2014.12.076 

Martinez Molina D, Jafari R, Ignatushcenko M, Seki T, et al. Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay. (2013) Science. DOI:10.1126/science.1233606 

Stefaniak J, Huber K.V.MImportance of Quantifying Drug-Target Engagement in Cells(2020) ACS. DOI: 10.1021/acsmedchemlett.9b00570 

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