Eligible Student Poster 49th Lorne Conference on Protein Structure and Function 2024

Targeted Protein Degradation: A Novel Target Deconvolution Method (#108)

Chuhui Ms Huang 1
  1. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Phenotypic screening has resurged in recent years due to its capability to identify first-in-class therapeutics compared to target-based screening. However, elucidating the target protein of the hit compound remains a challenge due to the complexity of the process and the technology required to identify the target protein from a myriad of proteins within the biological system. Chemoproteomics is one methodology widely applied today in target deconvolution. Nonetheless, target deconvolution remains a challenging and time-consuming undertaking, and orthogonal methodologies are required to confirm the results attained from proteomics. Targeted protein degradation is a new method in drug discovery based on a novel mechanism of action. Targeted protein degraders are able to knockdown or knockout target proteins in comparison to the conventional method of inhibiting protein targets. We envisage that targeted protein degradation has potential as a novel methodology to elucidate the target proteins of hits identified from phenotypic screen programs. Here, we present the design, synthesis and evaluation of novel chemical degrader probes targeting bromodomain-containing protein 4 (BRD4), which will assist with the development and validation of novel target deconvolution methods.