PROTAC Discovery and Development

Proteolysis-targeting chimera (PROTAC) has been developed as a therapeutic modality and a powerful research tool for targeted protein degradation. A heterobifunctional PROTAC molecule consists of three elements: a ligand that binds to the target protein (TP), a ligand that binds to E3 ubiquitin ligase, and a linker that conjugates these two ligands. PROTAC is a fast and reversible chemical knockdown strategy that degrades the target protein through ubiquitin-proteosome system. Upon binding to the target protein, the PROTAC recruits E3 for the TP ubiquitination, which results in proteasome-mediated degradation.

PROTAC technology offers many potential advantages. Different from competitive- and occupancy-driven process of traditional inhibitors, PROTAC molecules are catalytic in their mode of action. In this way, PROTACs can promote target protein degradation at relatively low exposures. PROTAC also has the potential to degrade the target pathogenic proteins and regulate signaling pathways that cannot be achieved by traditional therapy. Besides, PROTAC complements nucleic acid-based gene knockdown or out for targeted protein reduction and recapitulates biological activities of pharmacological proteins.

So far, as a novel approach, PROTAC has gained great attention from academia and the pharmaceutical/biotechnology industry. Many PROTAC molecules have been successfully developed and employed in the degradation of the target proteins related to various diseases, including cancer, immune disorders, viral infection, and neurodegenerative diseases. Some of them have already been under clinical trials. PROTAC has opened a new chapter for the development of new drugs and novel chemical knockdown tools. It has also brought unprecedented opportunities to the academia and industry.

Figure 1. Overview steps of entire protein degradation by PROTACs. Cited from ACS Med. Chem. Lett. 2020, 11, 3, 237-240

With integrated global resources, Profacgen provides a broad range of services for PROTAC discovery and development. It enables researchers to design and develop E3 ligase ligands, ligand-linker conjugates, target ligands, and intact PROTAC molecules effectively. Our services include:

• Ligand discovery and design
• E3 ligase/target protein development
• PROTAC in vitro evaluation
• PROTAC in vivo evaluation
• Structures and mechanism studies

With our state-of-the-art PROTAC platform, Profacgen offers researchers with highly customizable services to accelerate the degrader discovery progress. Please do not hesitate to contact us for more details. We are more than happy to generate a tailored quotation based on your specific requirements.