ArticleProceedings of the National Academy of Sciences of the United States of America2020
Discovery of potent thrombin inhibitors from a protease-focused DNA-encoded chemical library.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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
25 citing papers in PubMed, 74 citations in OpenAlex.
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Universal Baseline forbioRxiv : the preprint server for biology · 2026Article
- Biocatalytic- and Chemoproteomic-Guided Discovery of a PHGDH Inhibitor from Chemoenzymatic-Promoted DNA-Encoded Libraries Selection Platform.Journal of the American Chemical Society · 2025Article
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- DNA-encoded library screening uncovers potent DNMT2 inhibitors targeting a cryptic allosteric binding site.iScience · 2025Article
- Macrocyclic Phage Display for Identification of Selective Protease Substrates.Journal of the American Chemical Society · 2025Article
- PSA inhibitors for contraception: insights from prostate cancer.Trends in pharmacological sciences · 2025Review
- Evaluation of DNA encoded library and machine learning model combinations for hit discovery.npj drug discovery · 2025Article
- Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chemical Space Profiling of SARS-CoV-2 PLACS medicinal chemistry letters · 2024Article
- Mask and Release Strategy-Enabled Diversity-Oriented Synthesis for DNA-Encoded Library.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploiting the Carboxylate-Binding Pocket of β-Lactamase Enzymes Using a Focused DNA-Encoded Chemical Library.Journal of medicinal chemistry · 2024Article
- Small-molecule discovery through DNA-encoded libraries.Nature reviews. Drug discovery · 2023Review
- DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.Communications chemistry · 2023Article
- Using cancer proteomics data to identify gene candidates for therapeutic targeting.Oncotarget · 2023Article
- Combining pharmacophore models derived from DNA-encoded chemical libraries with structure-based exploration to predict Tankyrase 1 inhibitors.European journal of medicinal chemistry · 2023Article
- Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA-Displayed Peptide Libraries.Chembiochem : a European journal of chemical biology · 2022Review
- Converting Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded Libraries for More Versatile Selections.ACS omega · 2022Article
- DNA-Compatible Suzuki-Miyaura Cross-Coupling Reaction of Aryl Iodides With (Hetero)Aryl Boronic Acids for DNA-Encoded Libraries.Frontiers in chemistry · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
DNA-encoded chemical libraries are collections of compounds individually coupled to unique DNA tags serving as amplifiable identification barcodes. By bridging split-and-pool combinatorial synthesis with the ligation of unique encoding DNA oligomers, million- to billion-member libraries can be synthesized for use in hundreds of healthcare target screens. Although structural diversity and desirable molecular property ranges generally guide DNA-encoded chemical library design, recent reports have highlighted the utility of focused DNA-encoded chemical libraries that are structurally biased for a class of protein targets. Herein, a protease-focused DNA-encoded chemical library was designed that utilizes chemotypes known to engage conserved catalytic protease residues. The three-cycle library features functional moieties such as guanidine, which interacts strongly with aspartate of the protease catalytic triad, as well as mild electrophiles such as sulfonamide, urea, and carbamate. We developed a DNA-compatible method for guanidinylation of amines and reduction of nitriles. Employing these optimized reactions, we constructed a 9.8-million-membered DNA-encoded chemical library. Affinity selection of the library with thrombin, a common protease, revealed a number of enriched features which ultimately led to the discovery of a 1 nM inhibitor of thrombin. Thus, structurally focused DNA-encoded chemical libraries have tremendous potential to find clinically useful high-affinity hits for the rapid discovery of drugs for targets (e.g., proteases) with essential functions in infectious diseases (e.g., severe acute respiratory syndrome coronavirus 2) and relevant healthcare conditions (e.g., male contraception).
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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.