R & DPlatform Technology

The uSMITE™ (ubiquitin-mediated, Small Molecule Induced Target Elimination) platform technology is designed to expand the repertoire of E3 ligases used in targeted protein degraders and facilitate the creation of novel targeted protein degradation therapeutics.

What is an E3 ligase

E3 ligases are enzymes that catalyze the covalent attachment of ubiquitin molecules to target proteins, thereby marking them for degradation. Ubiquitinated proteins are then recognized and broken down by the proteasome complex within the cell.
Currently, most first-generation targeted protein degraders utilize either CRBN (cereblon) or VHL (von Hippel-Lindau tumor suppressor protein) as the recruiting E3 ligase. However, many E3 ligases, including CRBN and VHL, are not essential for cellular survival. Tumor cells can develop resistance to such degraders by mutating the genes that encode these ligases or suppressing their expression, thereby nullifying the effect of degraders that rely on them.

Advantages of uSMITE™

By leveraging its uSMITE™ technology, Cullgen has discovered multiple novel E3 ligands. Many of these ligands bind to previously unexplored E3 ligases, some of which are functionally essential and are therefore less likely to be downregulated by tumor cells. This provides a significant competitive advantage for targeted protein degraders in the oncology field.
Moreover, Cullgen has also identified E3 ligands that selectively bind to E3 ligases with tissue-specific expression or those highly expressed in tumors. By utilizing these ligands, Cullgen can develop degraders that act selectively in specific tissues or avoid action in others. Targeting E3 ligases that are highly expressed in tumors also allows for the design and development of safer and more effective targeted protein degraders.