Targeted protein degradation (TPD) is a novel approach used in drug discovery to effectively infiltrate cell’s proteasomal degradation pathway and quickly eliminate the target proteins from cells. This strategy has the potential to develop new therapeutics that differ considerably from classical inhibitors and is even viable for accessing “undruggable” protein targets and difficult-to-treat diseases.
Our diverse portfolio of protein degrader building blocks allows you to easily generate libraries of protein degraders that can be screened for an effective degradation of your target proteins from the cells. Our protein degraders, such as proteolysis targeting chimeras (PROTAC® molecules), are bifunctional molecules with three primary components:
Our protein degrader building blocks are permutations of the following components:
The simultaneous degrader binding of two proteins brings the POI in close enough proximity for polyubiquitination to take place by the E2 enzyme associated to the E3 ligase, which flags the POI for degradation through the proteasome.
The precise design of small-molecule target degraders is crucial for successful protein degradation. Even slight alterations in ligands and crosslinkers can affect binding to the POI or E3 ligase. Thus, many analogs are synthesized, varying each structure slightly, and screened in cells to determine the optimal degrader for target degradation.
Our degrader building blocks are a collection of crosslinker-E3 ligand conjugates with a pendant functional group for covalent linkage to a target ligand to streamline synthesis. Since the same functional group is present across a series, one target ligand can be conjugated to several degrader building blocks simultaneously for facile library generation and subsequent screening.
PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
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