Targeted Protein Degrader Building Blocks

The concurrent binding of a degrader molecule to two proteins—the protein of interest (POI) and an E3 ubiquitin ligase—enables the E3 ligase to recruit the E2 enzyme, initiating polyubiquitination of the POI. This post-translational modification flags the POI for targeted degradation via the proteasome, a central pathway in cellular regulation.

The design of effective PROTACs (proteolysis-targeting chimeras) demands precise control over linker length, shape, and attachment points to optimize binding affinity and functional efficacy. However, the heterobifunctional nature of PROTACs introduces considerable synthetic challenges, and computational tools often fall short in accurately predicting structure-activity relationships (SAR). Consequently, SAR exploration is primarily empirical, necessitating substantial investments of time and resources.

To address the challenges associated with PROTAC design and accelerate development, we have established a robust library of pre-formed E3-ligand linker intermediates. This resource enables the efficient synthesis of a wide array of diverse PROTAC candidates, facilitating their rapid evaluation and optimization for targeted protein degradation applications.