ArticleJournal of medicinal chemistry2017
Development of a Selective Inhibitor of Protein Arginine Deiminase 2.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 89 citations in OpenAlex.
- Mapping the Substrate Specificity Landscape of PAD2 and PAD4 Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Bibliometric and visualization analysis of arginine deiminase research from 2006 to 2025: trends, collaboration networks and emerging frontiers.Frontiers in immunology · 2026Article
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025Review
- Discovery of highly potent naphthalene/quinoline-based PAD inhibitors: Structure-activity relationship, selectivity, and cytotoxicity.European journal of medicinal chemistry · 2025Article
- Article
- Peptidylarginine Deiminase (PAD) Inhibitor Optimization through Displacement of a Trapped Water Molecule.ACS medicinal chemistry letters · 2025Article
- PAD2 disturbs cardiomyocyte calcium homeostasis by citrullinating SERCA2a protein in hemorrhagic shock induced arrhythmia.The journal of trauma and acute care surgery · 2025Article
- Citrullination of NF-κB p65 by PAD2 as a Novel Therapeutic Target for Modulating Macrophage Polarization in Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- New structural scaffolds to enhance the metabolic stability of arginine-derived PAD4 inhibitors.Results in chemistry · 2025Article
- Anticancer benzimidazole derivatives as inhibitors of epigenetic targets: a review article.RSC advances · 2025Review
- Targeting PADI2 as a potential therapeutic strategy against metastasis in oral cancer via suppressing EMT-mediated migration and invasion and CCL3/5-induced angiogenesis.Clinical & experimental metastasis · 2024Article
- Identification of novel PAD2 inhibitors using pharmacophore-based virtual screening, molecular docking, and MD simulation studies.Scientific reports · 2024Article
- A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.Nature communications · 2024Article
- Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity.IUCrJ · 2024Article
- Structure-Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy.Pharmaceutics · 2024Review
- Protein Citrullination in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases.Journal of experimental neurology · 2024Article
- The vacuolar anti-Frontiers in immunology · 2024Article
- AFM41a: A Novel PAD2 Inhibitor for Sepsis Treatment-Efficacy and Mechanism.International journal of biological sciences · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy (30a). Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.
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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.