Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
USP5 is widely distributed in various malignant tumors and can regulate the stability and promoting tumor progression of many tumor-related proteins. However, there is still a lack of highly active USP5 inhibitors. Therefore, effective inhibitors were screened in the TCMIO database in this study. Three hit compounds, CHEMBL3645368, CHEMBL3689818, and CHEMBL2070208, were finally obtained by molecular docking, molecular fingerprint, quantum chemistry, and molecular dynamics simulation. Molecular docking results showed hit compounds had similar binding mode comparing with positive compound. Quantum chemistry and molecular dynamics results showed hit compounds had better binding energy and higher affinity than the positive compound. ADMET predicted hit compounds had low toxicity. These results all suggest CHEMBL3645368, CHEMBL3689818, and CHEMBL2070208 may inhibit USP5 and could be candidates for further exploration.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10799893.2024.2443682 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovery of an exquisitely selective WDR5 chemical probe accelerated by a high-quality DEL-ML Hit.
RSC Chem Biol
July 2025
Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University Max-von-Laue-Str. 9 D-60438 Frankfurt am Main Germany
Herein we present the rapid development of LH168, a potent and highly selective chemical probe for WDR5, streamlined by utilizing a DEL-ML (DNA encoded library-machine learning) hit as the chemical starting point. LH168 was comprehensively characterized in bioassays and demonstrated potent target engagement at the WIN-site pocket of WDR5, with an EC of approximately 10 nM, a long residence time, and exceptional proteome-wide selectivity for WDR5. In addition, we present the X-ray co-crystal structure and provide insights into the structure-activity relationships (SAR).
View Article and Find Full Text PDFThe Influence of Single-Stranded or Double-Stranded DNA Tags on Ligand Binding Affinity in DNA-Encoded Libraries.
Anal Chem
September 2025
Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
DNA-encoded libraries have become widely used in drug discovery, and several different setups to link chemical compounds to DNA have been employed in the field, including single-stranded and double-stranded DNA tags as well as a variety of linker chemistries. In our previous study, we observed distinct differences in binding affinities between ligands coupled either to single-stranded or double-stranded DNA; however, the molecular basis for these differences remained unclear. Here, we present a native ion mobility mass spectrometry approach that incorporates gas- and solution-phase activation techniques to systematically investigate these differences, specifically the impact of DNA tags on binding performance in protein-ligand interactions.
View Article and Find Full Text PDFSertraline as a Scaffold for Antitrypanosoma Cruzi Drug Development: Design of Novel Derivatives and Computational Target Screening.
ChemMedChem
September 2025
Laboratorio de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, Caracas, 1041-A, Venezuela.
Due to the advantages of drug repurposing, the discovery of new chemotherapeutic agents for the treatment of Chagas disease based on approved drugs has become a strategy for identifying new candidates. In this work, the antidepressant drug sertraline is reported, with an IC of 7.8 ± 1.
View Article and Find Full Text PDFDiversity-Oriented C-H Activation Reactions of the Naphthalene Scaffold.
J Am Chem Soc
September 2025
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Diversity-oriented synthesis (DOS) has emerged as an efficient strategy for constructing diverse compound libraries, facilitating hit or lead identification in the drug discovery process. In parallel, developing diverse transformations at different sites is an appealing strategy to expand the diversity of appendages on scaffolds. Owing to the availability of C-H bonds at multiple sites of pharmacophores, diversity-oriented C-H activation reactions are an ideal approach to realize this goal.
View Article and Find Full Text PDFParallel synthesis of 5'-amino-5'-deoxy-adenosine derivatives for focused chemical space exploration and their application as methyltransferase inhibitors.
RSC Med Chem
August 2025
Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz Staudinger Weg 5 55128 Mainz Germany
Parallel syntheses and their throughput capabilities are powerful tools for the rapid generation of molecule libraries, making them highly beneficial for accelerating hit identification in early-stage drug discovery. Utilizing chemical spaces and virtual libraries enhances time and cost efficiency, enabling the faster exploitation of chemically diverse compounds. In this study, a parallel synthesis method for rapidly generating a 5'-amino-5'-deoxy adenosine-based amide and sulfonamide library of 42 compounds is described with high yields and purity, which is economical and ecological due to the reduced requirements for extensive purification.
View Article and Find Full Text PDF