Abstract

For a drug compound to be efficacious and safe, it must selectively bind to its intended target protein at the intended site of action. A significant portion of projects fail in the clinic due to lack of efficacy or failure to show that the drug candidate interacts with the intended target in a complex biological context. Too often, target engagement assessments are introduced late in drug discovery and development projects with increased risk of late-stage failures as a consequence. Applications of the proven CEllular Thermal Shift Assay (CETSA®) technology to assess target engagement in various matrixes are increasingly used for SAR studies and lead optimisation efforts. By the introduction of the high-throughput format, CETSA® Navigate HT, this technology has proven to be a powerful tool already in the hit identification phase. Due to its broad applicability to native, full length protein targets in the live cellular environment, without the need for expensive and time-consuming protein and/or compound labelling efforts, CETSA® Navigate HT may be regarded as a new paradigm for high-throughput screening.