Targeted protein degradation

KRAS G12D is an important driver mutation in solid tumors such as pancreatic, colorectal, and lung cancers. The emergence of molecules such as MRTX1133 has demonstrated that KRAS G12D can be directly targeted pharmacologically, whereas targeted protein degradation technologies such as PROTACs ...

Classical PROTACs rely on E3 ubiquitin ligases and the proteasome to eliminate intracellular target proteins, but they are difficult to apply to extracellular proteins, large-scale cellular components, and bacterial proteins. LYTAC, ATTEC, AUTAC, and BacPROTAC respectively utilize ...

Targeted protein degradation is expanding from the ubiquitin-proteasome system to the autophagy-lysosome system. AUTAC, AUTOTAC, and ATTEC can all exploit autophagy to eliminate specific targets, but they differ in cargo recognition and autophagy-recruitment mechanisms. First- and ...

Proteolysis-targeting chimeras (PROTACs) are a class of heterobifunctional molecules that selectively reduce the abundance of a protein of interest by harnessing the cellular ubiquitin–proteasome system (UPS). They represent an important modality within the field of targeted protein ...

The core question in targeted protein degradation is: “Can the cell be made to remove this protein, and can the removal process be proven to follow the expected mechanism?” Cellular protein levels are jointly regulated by synthesis, folding, localization, and degradation. The two systems ...

The anticancer drug Lenalidomide was once one of the world's top-selling small molecule drugs and orphan drugs, with sales of up to 9.978 billion US dollars in 2022, and its development company Celgene made huge profits.