OUR SCIENCE
OUR SCIENCE
Arvinas’ PROTAC Discovery Engine
Forging New Frontiers in Drug Discovery
From the founding of Arvinas in 2013 to the first PROTAC pivotal trial, 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 have demonstrated the ability to penetrate the blood-brain barrier
- First-in-human safety data
- First-in-human pharmacokinetic and pharmacodynamic data
- First-in-human efficacy data
Arvinas’ PROTAC Discovery Engine – The Proof is in the Pipeline
E3 KnowledgeBase
E3 KnowledgeBaseArvinas 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 PROTACs 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 protein-binding domains, including “undruggable” targets, and new binders for E3 ligases. Unlike traditional libraries, ours are designed specifically to facilitate incorporation into PROTACs and optimize their drug-like properties.
Deep understanding of the “Zone of Ubiquitination”
Understanding how ternary complexes form between PROTACs, 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 PROTACs to exploit this knowledge.
ANGLE: Arvinas Next Generation Linker Evolution
Our linkers incorporate all learnings from Arvinas’ long history of designing PROTACs, 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
PROTACs are often far more selective than the targeting protein-binding domain. 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
Arvinas RulesFor decades, the long-standing “Rule of 5” has guided small molecule discovery. We have discovered our own proprietary Arvinas Rules to create PROTACs 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 PROTACs with drug-like properties and activities.
If you’re inspired, please take a look at the current list of opportunities to join our team.
- 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.
- Arvinas LLC. Clinical Program Update: ARV-471 & ARV-110. December 14, 2020. New Haven, CT.
- Smits L, et al. First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of ARV-102, a PROTAC LRRK2 Degrader, in Healthy Volunteers. International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD); April 1–5, 2025; Vienna, Austria. 1963.
- Smits L, et al. First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ARV-102, a PROTAC LRRK2 Degrader, in Healthy Participants. International Congress of Parkinson’s Disease and Movement Disorders (MDS); October 5–9, 2025; Honolulu, HI USA. 904.
- Smits L, et al. First Clinical Trials of ARV-102, a PROTAC LRRK2 Degrader: Characterization of Pathway Engagement in Healthy Volunteers and Patients With Parkinson’s Disease. International Congress of Parkinson’s Disease and Movement Disorders (MDS); October 5–9, 2025; Honolulu, HI USA. LBA 22.
- Arvinas Presents First-in-Human Data for Investigational Oral PROTAC ARV-102 Demonstrating Blood-Brain Barrier Penetration, and Central and Peripheral LRRK2 Degradation. (Press Release, April 4, 2025).
- Arvinas Presents Late Breaking, Positive Phase 1 Clinical Data for ARV-102, a PROTAC LRRK2 Degrader, at the 2025 International Congress of Parkinson’s Disease and Movement Disorders®. (Press Release, October 5, 2025).