CETSA® can assess target engagement across a multitude of sample types. Established assays can easily be transferred from cell line to animal tissue, human primary cells, or patient–derived material, and thereby be used for translation all the way from lab bench to patient. By measuring the thermal shift induced by the compound binding to the protein, CETSA® can be used for assessing the target engagement potency and occupancy in tissue from animal studies or patient–isolated material. This will facilitate and expedite the evaluation of whether your compounds will have a therapeutic effect.
As CETSA® can be performed in live cells or tissue, the CETSA® EC50 values give you a consistent reference point that can enable translation as your compounds move from lead generation into lead optimization.
How does cellular target engagement relate to efficacy? Download our CETSA® Navigate application note.
In a report by Ishii et al., Takeda scientists used CETSA® for verifying in vivo target engagement (TE) of novel RIPK1 inhibitors in different sample matrices, such as spleen and brain. By using CETSA® alongside a semi-automated system, the researchers quantified the drug-target occupancy in mouse peripheral blood mononuclear cells. In addition, they were able to monitor the in vivo drug target engagement (TE) in spleen and brain tissue. This study demonstrates how CETSA® can be used to directly assess drug TE in in vivo animal experiments for lead optimization and highlights how you too could use CETSA® to enable more effective drug discovery.
Tsuyoshi Ishii, Takuro Okai, Misa Iwatani-Yoshihara, et al. CETSA quantitatively verifies in vivo target engagement of novel RIPK1 inhibitors in various biospecimens. (2017) Nature Scientific Reports. DOI: 10.1038/s41598-017-12513-1
”CETSA® data is a keystone in our SAR analysis, and by assessing cellular engagement of our compounds across multiple cell lines we gain confidence in our project prioritizations.”