Arvinas logo
Close this search box.

Our Science | PROTAC® Discovery Engine

PROTAC image close up

PROTAC® Discovery Engine

Forging New Scientific Frontiers in Drug Discovery

From the first paper on targeted protein degradation co-authored by Dr. Craig Crews of Yale University to Arvinas’ founding in 2013, we have firmly established ourselves as a leader in protein degradation research.

Our PROTAC® Discovery Engine has led to a robust pipeline, driving some of the most significant breakthroughs in targeted protein degradation within the industry:

  • Orally bioavailable degraders
  • Degraders that cross the blood-brain barrier in preclinical studies
  • First-in-human safety data
  • First-in-human pharmacokinetic and pharmacodynamic data
  • First-in-human efficacy data
PROTAC image close up
Arvinas scientific staffer reviewing specimen details on monitor

Arvinas’ PROTAC® Discovery Engine Is Different – the Proof is in the Pipeline

Our PROTAC® Discovery Engine creates clinical-stage programs with the potential to help patients: 

E3 KnowledgeBase

Arvinas has deep experience matching the right E3 ligase to the right target. The human body has more than 600 E3 ligases, and Arvinas is expanding our capabilities to include creating novel PROTAC® protein degraders that recruit E3 ligases with targeted expression patterns, such as tumor or central nervous system localized E3 ligases, where they may be beneficial for the development of targeted cancer and neurologic therapies.

Advanced screening capabilities

Arvinas has cutting-edge high-throughput and DNA-encoded library (DEL) screening abilities, powering our ability to identify new target-binding “warheads,” including “undruggable” targets, and new binders for E3 ligases. Unlike traditional libraries, ours are designed specifically to facilitate incorporation into PROTAC® protein degraders and optimize their drug-like properties.

Deep understanding of the “Zone of Ubiquitination”

Understanding how ternary complexes form between PROTAC® protein degraders, target proteins, and E3 ligases is necessary but not sufficient. At Arvinas, we use structural and biochemical information to predict precisely which lysine residues on the target protein can be “tagged” with ubiquitin, and we design PROTAC® degraders to exploit this knowledge.

ANGLE: Arvinas Next Generation Linker Evolution

Our privileged linkers incorporate all learnings from Arvinas’ long history of designing PROTAC® protein degraders, allowing increased potency and selectivity right from the start.

Predictive computational modeling

With our deep experience in trimer structure-based computational modeling and design algorithms, we frequently create potent degraders in the first chemical series.

State-of-the-art proteomics capabilities

A PROTAC® protein degrader is often far more selective than the targeting warhead. Our proteomics capabilities enable us to understand that specificity in precise detail and iterate quickly to optimize the selectivity of our degraders for the drug target.

Arvinas Rules

For decades, the long-standing “Rule of 5” has guided small molecule discovery. We have discovered our own proprietary Arvinas Rules to create PROTAC® protein degraders that, for example, are orally bioavailable and cross the blood-brain barrier.

Deep knowledge of in vivo PK/PD and efficacy relationships

Our comprehensive understanding of molecular features that impact PROTAC® biodistribution and target degradation in the body enables us to create PROTAC® protein degraders with drug-like properties and activities.

Smiling Arvinas scientific staff member talking with colleague
Arvinas scientific staff

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

  1. Cacace, A. Discovery of Brain Penetrant PROTAC Degrader Molecules That Target Pathologic Tau and alpha-Synuclein Protein Species. Presented at: Targeted Protein Degradation Summit. October 24, 2019. Boston, MA.
  2. Arvinas LLC. Clinical Program Update: ARV-471 & ARV-110. December 14, 2020. New Haven, CT. 
  3. Cacace, A. Discovery of Brain Penetrant PROTAC Degrader Molecules That Target Pathologic Tau and alpha-Synuclein Protein Species. Presented at: Targeted Protein Degradation Summit. October 24, 2019. Boston, MA.


You are now leaving Arvinas does not endorse or recommend the content in any third-party sites. Arvinas is not responsible and disclaims liability for the content, or for any viruses or similar harmful programs, that may be present on third-party pages or sites. Visits to a third-party website are at your own risk and subject to the terms and conditions and privacy policy of such site.

Skip to content