Focusing on Relevance: CETSA-Guided Medicinal Chemistry and Lead Generation.

Confirmation of target engagement in relevant physiological environment ensures successful drug discovery and the right project prioritization. The Cellular Thermal Shift Assay (CETSA) offers a robust label-free method for studying protein-compound interactions in a cellular environment. This Viewpoint covers the broad applicability of CETSA in lead generation. The method can be used for deconvolution studies, target validation, screening of compound libraries, and hit confirmation. Moreover, the method is well suited for generation of relevant structure-activity relationship (SAR) data, enabling optimal compound design.