ArticleACS chemical biology2023
Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach.
Article in ACS chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 51 citations in OpenAlex.
- A Versatile DNA-Encoded Library Platform for the Discovery of Highly Cooperative Chemical Inducers of Proximity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PhenoDEL: A Novel Screening Strategy Based on Intracellular Protein Degradation Activity.ACS chemical biology · 2026Article
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- Methods to accelerate PROTAC drug discovery.The Biochemical journal · 2025Review
- A method to identify small molecule/protein pairs susceptible to protein ubiquitination by the CRBN E3 ligase.Chemical science · 2025Article
- Evaluation of DNA encoded library and machine learning model combinations for hit discovery.npj drug discovery · 2025Article
- Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.Cell chemical biology · 2025Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Characteristic roadmap of linker governs the rational design of PROTACs.Acta pharmaceutica Sinica. B · 2024Review
- Highly Selective Novel Heme Oxygenase-1 Hits Found by DNA-Encoded Library Machine Learning beyond the DEL Chemical Space.ACS medicinal chemistry letters · 2024Article
- Building Block-Centric Approach to DNA-Encoded Library Design.Journal of chemical information and modeling · 2024Article
- DNA-encoded library-enabled discovery of proximity-inducing small molecules.Nature chemical biology · 2024Article
- Affinity for both sides.Nature chemical biology · 2024Article
- Recognition and reprogramming of E3 ubiquitin ligase surfaces by α-helical peptides.Nature communications · 2023Article
- Rational Screening for Cooperativity in Small-Molecule Inducers of Protein-Protein Associations.Journal of the American Chemical Society · 2023Article
- Small-molecule discovery through DNA-encoded libraries.Nature reviews. Drug discovery · 2023Review
- Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteolysis targeting chimera (PROTAC) strategy results in the down-regulation of unwanted protein(s) for disease treatment. In the PROTAC process, a heterobifunctional degrader forms a ternary complex with a target protein of interest (POI) and an E3 ligase, which results in ubiquitination and proteasomal degradation of the POI. While ternary complex formation is a key attribute of PROTAC degraders, modification of the PROTAC molecule to optimize ternary complex formation and protein degradation can be a labor-intensive and tedious process. In this study, we take advantage of DNA-encoded library (DEL) technology to efficiently synthesize a vast number of possible PROTAC molecules and describe a parallel screening approach that utilizes DNA barcodes as reporters of ternary complex formation and cooperative binding. We use a designed PROTAC DEL against BRD4 and CRBN to describe a dual protein affinity selection method and the direct discovery of novel, potent BRD4 PROTACs that importantly demonstrate clear SAR. Such an approach evaluates all the potential PROTACs simultaneously, avoids the interference of PROTAC solubility and permeability, and uses POI and E3 ligase proteins in an efficient manner.
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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.