Protein Degradation and Resources
rotein degradation is the process by which proteins are naturally destroyed in a cell in order to maintain protein homeostasis, or an equilibrium of proteins in the human body. The body is constantly making and remaking proteins (creation), while also removing ones that have become inactive or mutated (degradation). When a cell is unable to degrade certain proteins, the proteins can accumulate, causing diseases like cancer. With targeted protein degradation, researchers are harnessing the cell’s own machinery to degrade several whole new classes of proteins that were previously considered “undruggable.”
Protein degradation is a core strength for Bristol Myers Squibb, having launched multiple successful protein degrader agents. With several protein degraders in clinical trials, developed based on decades of unique research and clinical experience, Bristol Myers Squibb is building on its legacy and scientific expertise. Unlike early protein degradation agents that were initially developed upon observation of their effects, these newer agents are being developed from discovery to clinic to achieve their pharmacologic effect with a specific mechanism of action and may potentially address a broader range of diseases, alone or in combination with other therapeutics.
Researchers at Bristol Myers Squibb are leveraging two different methods of protein degradation: molecular glues (cereblon E3 ligase modulators, CELMoD® agents) and heterobifunctional agents (also called ligand-directed degraders, or LDDs).
- CELMoD agents are molecules that act as molecular glue to alter the protein-binding properties of cereblon (an important component of the protein degradation cellular machinery) to promote interaction with and degradation of disease-causing proteins.
- LDDs are 3-part molecules (two ends joined by a linker) engineered to link target proteins with key components of the protein degradation cellular machinery, redirecting the machinery to degrade the target proteins.
Learn more about the science behind protein degradation and ongoing research at Bristol Myers Squibb.