ArticleJournal of medicinal chemistry2015
Design, synthesis, and biological evaluation of tetrazole analogs of Cl-amidine as protein arginine deiminase inhibitors.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 93 citations in OpenAlex.
- Article
- Peptidylarginine Deiminase (PAD) Inhibitor Optimization through Displacement of a Trapped Water Molecule.ACS medicinal chemistry letters · 2025Article
- Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025Review
- Inhibiting peptidylarginine deiminases (PAD1-4) by targeting a CaNature communications · 2025Article
- Exploring tetrazole chemistry: synthetic techniques, structure-activity relationship, and pharmacological insights in antimicrobial and anticancer therapy.Frontiers in chemistry · 2025Review
- Structure-Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy.Pharmaceutics · 2024Review
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Neutrophil extracellular traps in autoimmune diseases: Analysis of the knowledge map.Frontiers in immunology · 2023Article
- Enhanced catalysis through structurally modified hybrid 2-D boron nitride nanosheets comprising of complexed 2-hydroxy-4-methoxybenzophenone motif.Scientific reports · 2021Article
- Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles.Chemical science · 2021Article
- Chemical biology of protein citrullination by the protein A arginine deiminases.Current opinion in chemical biology · 2021Review
- Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.Journal of medicinal chemistry · 2020Review
- Chromatin interactions reveal novel gene targets for drug repositioning in rheumatic diseases.Annals of the rheumatic diseases · 2019Article
- Protein Arginine Deiminases (PADs): Biochemistry and Chemical Biology of Protein Citrullination.Accounts of chemical research · 2019Article
- Peptidylarginine Deiminases Post-Translationally Deiminate Prohibitin and Modulate Extracellular Vesicle Release and MicroRNAs in Glioblastoma Multiforme.International journal of molecular sciences · 2018Article
- Synthesis and Biological Evaluation of an Indazole-Based Selective Protein Arginine Deiminase 4 (PAD4) Inhibitor.ACS medicinal chemistry letters · 2018Article
- Sustainable Generation of Ni(OH)ACS omega · 2018Article
- Tumor-Derived Exosomes Induce the Formation of Neutrophil Extracellular Traps: Implications For The Establishment of Cancer-Associated Thrombosis.Scientific reports · 2017Article
- 10 Years of GWAS Discovery: Biology, Function, and Translation.American journal of human genetics · 2017Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of arginine residues to form citrulline. This once obscure modification is now known to play a key role in the etiology of multiple autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, lupus, and ulcerative colitis) and in some forms of cancer. Among the five human PADs (PAD1, -2, -3, -4, and -6), it is unclear which isozyme contributes to disease pathogenesis. Toward the identification of potent, selective, and bioavailable PAD inhibitors that can be used to elucidate the specific roles of each isozyme, we describe tetrazole analogs as suitable backbone amide bond bioisosteres for the parent pan PAD inhibitor Cl-amidine. These tetrazole based analogs are highly potent and show selectivity toward particular isozymes. Importantly, one of the compounds, biphenyl tetrazole tert-butyl Cl-amidine (compound 13), exhibits enhanced cell killing in a PAD4 expressing osteosarcoma bone marrow (U2OS) cell line and can also block the formation of neutrophil extracellular traps. These bioisosteres represent an important step in our efforts to develop stable, bioavailable, and selective inhibitors for the PADs.
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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.