PROTAC Platforms

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional molecules that consist of three parts: an E3 ligand that binds to an E3 ligase, a ligand that binds to the protein of interest, and a linker connecting two ligands. PROTACs bring the target protein and the endogenous E3 ligases into close proximity, resulting in target protein ubiquitination and degradation. Moreover, PROTAC itself will not be degraded in this process and can be recycled, which makes PROTAC a valuable tool for studying protein degradation. This technique allows for the degradation of proteins closely associated with disease and has many advantages over traditional protein inhibition.

Focusing on the huge potential of PROTAC in drug development, the Protein Chemistry Department of Profacgen has established a powerful PROTAC platform, established the compound library of highly affinity small molecules and small molecule fragments of popular targeted proteins, analyzed a wide range of E3 ligase highly affinity small molecules and small molecule fragments, and designed the PROTAC model of linker system and non-linker system. These accumulated compound libraries can be used for rapid and efficient ligand and targeting protein design, greatly improving the drug development process of PROTAC.

Figure 1. Mode of action of PROTACs (Sun, X.Y.; et al. 2019)

Services

The PROTAC platform established by Profacgen is constantly expanding, aiming to provide end-to-end professional services to clients all over the world. We have recruited experienced PROTAC experts to perfect and optimize different PROTAC systems in all aspects. For different projects, we can customize efficient workflows to ensure the optimal design of PROTAC. Our teams have successfully identified Hits and leads across several projects, including those that moving into preclinical development through strong collaborative efforts. Our platform is expanding to support HaloPROTAC, ATTEC, AUTAC, and LYTAC.

• HaloPROTAC: HaloPROTAC system uses HaloTag protein to covalently conjugate chloroalkane labeled molecules with the target fusion protein. We provide powerful HaloPROTAC development service.
• ATTEC: In contrast to PROTAC and AUTAC, ATTEC molecules are independent of ubiquitination, which based on LC3 protein, is a novel target protein degrade strategy that based on the macroautophagy/autophagy pathway.
• AUTAC: Rely on autophagy, AUTAC (autophagy-targeting chimera) degrades a wider range of substrates by triggering K63 polyubiquitination, especially suitable for degrading target proteins in cytoplasm that are resistant to PROTAC molecule.
• LYTAC: LYTAC targets proteins of interest for degradation through lysosomal degradation pathways such as EGFR degradation pathway. In comparison to PROTAC, LYTAC can target extracellular and membrane-associated proteins using conjugates that bind both a cell-surface lysosome-shuttling receptor and the extracellular domain.

Profacgen has accumulated lots of experience PROTAC. Our professional technical team can provide customers with various PROTAC systems according to your project. Our competitive prices and extensive expertise have earned us the trust of our collaborators. Contact us to find out how Profacgen could be of assistance.

Reference

1. Sun, X.Y.; et al. PROTACs: great opportunities for academia and industry. Signal Transduction and Targeted Therapy. 2019.