ArticleJournal of the American Chemical Society2022
Bridged Proteolysis Targeting Chimera (PROTAC) Enables Degradation of Undruggable Targets.
Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 116 citations in OpenAlex.
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- An EZH2-SREBP2 axis promotes cholesterol biosynthesis and represents a noncanonical vulnerability in tumorigenesis.Nature cell biology · 2026Article
- Proteolysis‑targeting chimeras in oral squamous cell carcinoma: Current evidence, translational challenges and future directions (Review).Molecular medicine reports · 2026Review
- Tricarbonyl Rhenium-Based PROTACs Degrade the SARS-CoV-2 Mpro Protease.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Engineering Polymeric Nano-PROTAC for Targeted Protein Degradation and Cancer Therapy.Polymer science & technology (Washington, D.C.) · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.Journal of medicinal chemistry · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Ubiquitin-dependent degradation of p27Kip1 and p21Waf1/Cip1 by AMBRA1 ensures G1 and S phase progression and limits replication stress.Nucleic acids research · 2026Article
- Carborane Hydrophobic Tags Drive Selective Degradation of Endogenous KRASACS bio & med chem Au · 2026Article
- Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets.Biomarker research · 2026Review
- Discovery of a selective CDK7 PROTAC against acute leukemia with low platelet toxicity.Leukemia · 2026Article
- Article
- PROTACs for Collateral Degradation: Is It Time to Back Up the Bus?ACS medicinal chemistry letters · 2026Review
- Ubiquitin-Modifying Enzymes as Cell-Fate Regulators in Intestinal Inflammation.International journal of biological sciences · 2026Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Contemporary Developments in PROTACs for Cancer Management: An In-Depth Review.Current topics in medicinal chemistry · 2026Review
- E3 ubiquitin ligases in neurodegenerative diseases.Military Medical Research · 2026Review
- Evolution of proteolysis-targeting chimeras (PROTAC) technology to overcome challenges of antimicrobial resistance.npj antimicrobials and resistance · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Proteolysis Targeting Chimeras (PROTACs) are attractive therapeutic modalities for degrading disease-causing proteins. While many PROTACs have been developed for numerous protein targets, current small-molecule PROTAC approaches cannot target undruggable proteins that do not have small-molecule binders. Here, we present a novel PROTAC approach, termed bridged PROTAC, which utilizes a small-molecule binder of the target protein's binding partner to recruit the protein complex into close proximity with an E3 ubiquitin ligase to target undruggable proteins. Applying this bridged PROTAC strategy, we discovered MS28, the first-in-class degrader of cyclin D1, which lacks a small-molecule binder. MS28 effectively degrades cyclin D1, with faster degradation kinetics and superior degradation efficiency than CDK4/6, through recruiting the CDK4/6-cyclin D1 complex to the von Hippel-Lindau E3 ligase. MS28 also suppressed the proliferation of cancer cells more effectively than CDK4/6 inhibitors and degraders. Altogether, the bridged PROTAC strategy could provide a generalizable platform for targeting undruggable proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.