ArticleACS medicinal chemistry letters2023
Rapid PROTAC Discovery Platform: Nanomole-Scale Array Synthesis and Direct Screening of Reaction Mixtures.
Article in ACS medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Syndirella: synthesis-directed fragment elaboration enables extensive and cost-effective binding site exploration beyond catalog compounds.Chemical science · 2026Article
- Accelerate Your Science: Direct-to-Biology Strategies in Medicinal Chemistry.Journal of medicinal chemistry · 2026Review
- A Direct-to-Biology Amine-Acid Amination for Rapid Phenotypic Profiling of Lysosomotropic Natural Products.Journal of the American Chemical Society · 2026Article
- Development of a Direct-to-Biology Platform to Discover Potent MNK Inhibitors.Journal of medicinal chemistry · 2026Article
- Nanoscale Direct-to-Biology Optimization of Cdk2 Inhibitors.Journal of medicinal chemistry · 2026Article
- Alkyne Two-Phase Strategy: Rapid Generation of TK-285-Derived PROTACs as BRD4 Degraders.Journal of medicinal chemistry · 2026Article
- A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.Nature communications · 2026Article
- Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery.ChemMedChem · 2026Review
- Click. Screen. Degrade. A Miniaturized D2B Workflow for Rapid PROTAC Discovery.Journal of medicinal chemistry · 2026Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- Nanoscale Direct-to-Biology Optimization and Structural Insights into SelectiveJournal of medicinal chemistry · 2025Article
- High-Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15-Specific Protease mUSP18.Angewandte Chemie (International ed. in English) · 2025Article
- Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening.Nature communications · 2025Article
- Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs.Communications chemistry · 2025Review
- PROTAC-Based Antivirals for Respiratory Viruses: A Novel Approach for Targeted Therapy and Vaccine Development.Microorganisms · 2025Review
- Methods to accelerate PROTAC drug discovery.The Biochemical journal · 2025Review
- Workflow for E3 Ligase Ligand Validation for PROTAC Development.ACS chemical biology · 2025Article
- Property-based optimisation of PROTACs.RSC medicinal chemistry · 2025Article
- Factors to Consider for Synthesis in 1536-Well Plates─An Amide Coupling Case Study for PROTAC Synthesis.The Journal of organic chemistry · 2025Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Precise length, shape, and linker attachment points are all integral components to designing efficacious proteolysis targeting chimeras (PROTACs). Due to the synthetic complexity of these heterobifunctional degraders and the difficulty of computational modeling to aid PROTAC design, the exploration of structure-activity relationships remains mostly empirical, which requires a significant investment of time and resources. To facilitate rapid hit finding, we developed capabilities for PROTAC parallel synthesis and purification by harnessing an array of preformed E3-ligand-linker intermediates. In the next iteration of this approach, we developed a rapid, nanomole-scale PROTAC synthesis methodology using amide coupling that enables direct screening of nonpurified reaction mixtures in cell-based degradation assays, as well as logD and EPSA measurements. This approach greatly expands and accelerates PROTAC SAR exploration (5 days instead of several weeks) as well as avoids laborious and solvent-demanding purification of the reaction mixtures, thus making it an economical and more sustainable methodology for PROTAC hit finding.
Identifiers
What OpenQuestion holds
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.