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Protein degraders, from clinic to crops

Bayer and Arvinas have joined forces to develop a new class of agents that degrade proteins rather than inhibit them. The overall deal, announced on June 4, includes $110 million in upfront cash to work with Arvina’s protein-degrading PROTAC (PROteolysis-TArgeting Chimeras) technology to find new therapeutics for cardiovascular, oncology and gynecology indications. The deal also extends to agricultural uses, with Bayer and Arvinas launching a Crop Science joint venture. The aim is to develop novel protein-degrading molecules to fight weeds, insects and other agricultural pests. Unlike traditional small molecules that aim to inhibit the target protein’s active site, Arvina’s PROTACs harness the ubiquitin proteasome system to destroy the target molecule. PROTACs are bifunctional small molecules that use one arm to bind a target and the other to bind an E3 ubiquitin ligase. Once a PROTAC brings together the target protein and the E3 ligase, the enzyme ubiquitinates the target protein, tagging it for disposal. In agriculture, PROTAC technology also has the potential to rekindle crop-protection mechanisms that have become ineffective due to resistance, according to Bayer. Other companies focused on targeted degrader chemistries for clinical applications include C4 Therapeutics and Kymera Therapeutics. In April, Arvinas became the first company to take this approach to the clinic, when it began dosing patients in a phase 1 trial for the treatment of metastatic castration-resistant prostate cancer with the drug ARV-110. Results are expected in the second half of 2019. The company also has plans for testing this drug against breast cancer, and a phase 1 clinical trial planned for the third quarter of 2019.

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Protein degraders, from clinic to crops. Nat Biotechnol 37, 701 (2019).

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