Cellular Thermal Shift Assay (CETSA) is a method of identifying protein-drug interactions by monitoring changes in protein thermal stability. CETSA is traditionally performed by using Western Blotting to examine the thermal stability shifts of a single protein of interest. By combining CETSA with Mass Spectrometry the shifts in thermal stability can be examined for an entire proteome in a single experiment in a technique known as CETSA-MS or Thermal Proteome Profiling (TPP). This can be used to identify targets of a compound of interest in order to further understand the compounds mechanism of interest, potentially making CETSA a powerful tool for target discovery. Here we attempt to develop a protocol by which CETSA can be used as a drug target discovery tool. Our work has allowed us to create a protocol that can reliably identify soluble drug targets. Our results demonstrate the capacity of CETSA to screen multiple compounds as well as to perform more in depth dose response studies, and highlight how future improvements could be made to the protocol

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