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We Invented PROTAC® Targeted Protein Degraders

Arvinas’ PROTAC® targeted protein degraders, or proteolysis-targeting chimeras, harness the body’s natural protein disposal system to destroy disease-causing proteins.

In the 20 years since Arvinas founder Dr. Craig Crews of Yale University co-authored the first paper on targeted protein degradation, Arvinas has continued to advance and evolve this novel technology.

Across multiple diseases, our clinical data to date validates our research platform and targets.

Arvinas scientific staff members preparing vials for testing
PROTAC molecule
Arvinas scientific staff member preparing vials for testing

Using Induced Proximity to Leverage the Cell’s Natural Degradation Machinery

Induced proximity is a novel approach to tackling difficult-to-drug targets and diseases by developing medicines that act like molecular matchmakers by bringing two things together. Instead of trying to grapple with difficult targets on their own, induced proximity medicines mobilize biological mechanisms to do the heavy lifting.

The proteasome is the “garbage disposal” of the cell. PROTAC® protein degraders induce targeted protein degradation, selecting disease-causing proteins to be sent to the proteasome, using the cell’s natural method for removing problematic proteins.

Conventional drugs require tight binding to their targets in order to work. PROTAC® protein degraders are more durable and versatile, as they do not need to bind tightly to their targets and can act in a catalytic fashion, inducing the sequential degradation of multiple copies of the target protein.

Advantages of PROTAC®- mediated protein degradation

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The Potential to Target the “Undruggable”

Traditional small molecule inhibitors often require strong binding to a target protein, frequently to its active site. Since PROTAC® protein degraders only need to bind weakly to the target protein in order to specifically “tag” it, the ~80% of the proteome that is currently “undruggable” may be addressable by PROTAC® protein degraders. Since the PROTAC® degrader is not destroyed as it targets disease-causing proteins for elimination, it can act in an iterative or “catalytic” fashion, inducing the sequential degradation of multiple copies of the target protein

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Multiple routes of administration

We can generate PROTAC® protein degraders to be delivered orally, via injection, or via infusion, depending on the disease and need.

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Broad distribution in the body

In contrast to some other novel modalities, PROTAC® protein degraders have broad distribution in the body and can be manufactured using well-understood processes.

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Crossing the blood/brain barrier

In preclinical studies, our PROTAC® protein degraders have successfully penetrated the blood-brain barrier, a key step in developing drugs to treat neurodegenerative diseases.

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Tissue-specific targeting

Unlike other small molecules, the activity of a PROTAC® protein degrader can be targeted to a specific tissue by recruiting an E3 ligase which is expressed only in that cell lineage.

Proof of Concept Against Two Disease-Causing Target Proteins

We are the first targeted protein degradation company to develop a therapeutic modality that has shown early efficacy signals in patients with prostate and breast cancers.

Arvinas currently has two compounds that will soon enter pivotal trials, bavdegalutamide (ARV-110) for the potential treatment of men with metastatic castration-resistant prostate cancer and ARV-471 for the treatment of patients with locally advanced or metastatic estrogen receptor (ER) positive / human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

In addition to our oncology pipeline, we are developing targeted protein degraders against neurodegenerative diseases.

The agents listed above are currently under investigation. Their safety and effectiveness have not yet been established.

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Arvinas scientific staff preparing materials for testing
Smiling Arvinas scientific staff member talking with colleagues

If you’re inspired, please take a look at the current list of opportunities to join our team.


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