(1051-D) Leveraging high throughput targeted proteomics to impact a protein degrader project at AstraZeneca
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Targeted proteomics leverages high precision and quantitative accuracy for a set of target protein(s), affording higher throughput as opposed to discovery proteomics. Our group has made advancements to increase the speed in both sample preparation as well as decreasing the data collection time on the mass spectrometer for faster turnaround. For degrader projects, this method is immensely valuable for understanding compound dependent degradation in-cell and in vivo. This poster describes one particular case study of targeted proteomics applications in a protein degrader project in Oncology at AstraZeneca. Due to the non-specificity of the particular antibody used for this program, targeted proteomics provided a key alternative method to understand accurate DC50 and Dmax values for monovalent degraders. Additionally, the protein degradation, as opposed to inhibition, was correlated with potency in the phenotypic readout. Finally, targeted proteomics was instrumental in the in vivo cascade as the highest throughput method available for assessing PD. The method provided an understanding of protein degradation as a function of dose and time. In conclusion, targeted proteomics has provided an effective in-cell and in vivo PD readout for a protein degrader project at AstraZeneca.