Report: E3 Ligases, Long Seen as Challenging, Hold Immense Potential

Targeted Protein Degradation Seeing Renewed Optimism in Research Field

April 30, 2019

WELLESLEY, Mass., April 30, 2019–Global interest in ubiquitin proteasome systems is growing as researchers find new fields of research to pursue and probe unexplored strategies, according to a report by BCC Research.

Targeted protein degradation, in particular, is renewing optimism in what was once a field full of “garbage proteins,” according to the report “Nothing Degrading about Saving Lives: E3 Ligands Recruiting New Drugs.”

Major players in the market include Biogen (BIIB), Eisai (4523), Novartis (NOVN), Roche (ROG), AC Immune (ACIU) and Eli Lilly (LLY).

Research Highlights

  • C4 Therapeutics has lucrative pacts with Roche and Calico, Alphabet’s life sciences arm.
  • Novartis is working on degraders through a collaboration with the University of California, Berkeley.
  • In 2018, Celgene and Evotec partnered in drug discovery to focus on targeted protein degradation. The partners will use Evotec's Panomics platform, which integrates genomic, transcriptomic, and proteomic data for analysis with the company's PanHunter bioinformatic technology to identify difficult-to-track drug targets.

“Although it is obviously exciting that E3 ligases are revived as a drug target in drug discovery, more importantly it brings a possibility to develop drugs against very challenging proteins,” notes report author Marianna Tcherpakov. “One very ‘difficult’ target is tau protein related to Alzheimer’s. Solubilizing or degrading protein plaques is not a trivial mission, therefore systems like PROTAC represent an opportunity to overcome disadvantages of previous technologies.”

Work by Arvinas to Create a New Class of Drugs

Arvinas is developing a new class of drugs that engages the body’s own natural protein disposal system to treat cancers and other difficult diseases. As a potential improvement over traditional small molecule inhibitors, proteolysis-targeting chimera protein degraders are able to degrade disease-causing proteins through the cell’s ubiquitin proteasome system, which routinely degrades proteins. This is just one example of companies using targeted protein degradation platforms in drug discovery.

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Nothing Degrading about Saving Lives: E3 Ligands Recruiting New Drugs( PHM192A )
Publish Date: Apr 2019    

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