Peptidylarginine deiminases 4 as a promising target in drug discovery

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

(2021) Johannes Klopf et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

PAD4 takes charge during neutrophil activation: Impact of PAD4 mediated NET formation on immune‐mediated disease

(2021) Xiaosong Liu et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides

(2021) Izzuddin Ahmad Nadzirin et al.   COMPUTATIONAL BIOLOGY AND CHEMISTRY

The human cathelicidin LL-37 is a nanomolar inhibitor of amyloid self-assembly of islet amyloid polypeptide (IAPP)

(2020) Valentina Armiento et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

(2020) Chih-Cheng Lai et al.   INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

(2020) Pinar Uysal-Onganer et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Citrullination Alters the Antiviral and Immunomodulatory Activities of the Human Cathelicidin LL-37 During Rhinovirus Infection

(2020) Víctor Casanova et al.   Frontiers in Immunology

CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

(2020) Álvaro Teijeira et al.   IMMUNITY

Targeting potential drivers of COVID-19: Neutrophil extracellular traps

(2020) Betsy J. Barnes et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis

(2020) Lai Shi et al.   MOLECULAR CANCER RESEARCH

A novel peptidylarginine deiminase 4 (PAD4) inhibitor BMS-P5 blocks formation of neutrophil extracellular traps and delays progression of multiple myeloma

(2020) Marina Li et al.   MOLECULAR CANCER THERAPEUTICS

PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets

(2020) Ashley M. Curran et al.   Nature Reviews Rheumatology

NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture

(2020) Hawa Racine Thiam et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke

(2020) Lijing Kang et al.   Nature Communications

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

(2020) Xiaoyan Liu et al.   Acta Pharmaceutica Sinica B

Evaluation of protein arginine deiminase-4 inhibitor in TNBS- induced colitis in mice

(2020) Tingting Zhang et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

The roles of PAD2 ‐ and PAD4 ‐mediated protein citrullination catalysis in cancers

(2020) Yanbin Wang et al.   INTERNATIONAL JOURNAL OF CANCER

TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors

(2020) Songlin Song et al.   International Journal of Nanomedicine

The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis

(2020) Maria Teresa Masucci et al.   Frontiers in Immunology

Citrullination-Resistant LL-37 Is a Potent Antimicrobial Agent in the Inflammatory Environment High in Arginine Deiminase Activity

(2020) Danuta Bryzek et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Neutrophil extracellular traps are induced in a psoriasis model of interleukin-36 receptor antagonist-deficient mice

(2020) Soichiro Watanabe et al.   Scientific Reports

Systemic levels of anti-PAD4 autoantibodies correlate with airway obstruction in cystic fibrosis

(2019) Ruchi Yadav et al.   Journal of Cystic Fibrosis

Neutrophil Extracellular Traps in Arterial and Venous Thrombosis

(2019) Elodie Laridan et al.   SEMINARS IN THROMBOSIS AND HEMOSTASIS

Therapeutic Targeting of Neutrophil Extracellular Traps in Atherogenic Inflammation

(2019) Lars Maegdefessel et al.   THROMBOSIS AND HAEMOSTASIS

Synthesis of reversible PAD4 inhibitors via copper-catalyzed C−H arylation of benzimidazole

(2019) Zhengwei Guo et al.   Science China-Chemistry

Citrullination in Cancer

(2019) Arseniy E. Yuzhalin   CANCER RESEARCH

Discovery of Novel Potential Reversible Peptidyl Arginine Deiminase Inhibitor

(2019) Ardita Aliko et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

(2019) Carlos Silvestre-Roig et al.   NATURE

Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis after Vessel Injury

(2019) Nicoletta Sorvillo et al.   CIRCULATION RESEARCH

Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk

(2019) Shuai Shao et al.   Frontiers in Immunology

Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth

(2019) Hamza O Yazdani et al.   CANCER RESEARCH

Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis

(2019) MK Jonsson et al.   SCANDINAVIAN JOURNAL OF RHEUMATOLOGY

Compromised Anti-inflammatory Action of Neutrophil Extracellular Traps in PAD4-Deficient Mice Contributes to Aggravated Acute Inflammation After Myocardial Infarction

(2019) Kaveh Eghbalzadeh et al.   Frontiers in Immunology

MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps

(2019) Avin Hawez et al.   Frontiers in Immunology

Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction

(2019) Mingjun Du et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Novel Role of IL (Interleukin)-1β in Neutrophil Extracellular Trap Formation and Abdominal Aortic AneurysmsHighlights

(2018) Akshaya K. Meher et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G

(2018) Eduardo J. Folco et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Augmented neutrophil extracellular traps formation promotes atherosclerosis development in socially defeated apoE −/− mice

(2018) Keita Yamamoto et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis

(2018) Milka Koupenova et al.   CIRCULATION RESEARCH

Inhibition of peptidylarginine deiminase alleviates LPS-induced pulmonary dysfunction and improves survival in a mouse model of lethal endotoxemia

(2018) Yingjian Liang et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Peptidylarginine deiminase 4: a nuclear button triggering neutrophil extracellular traps in inflammatory diseases and aging

(2018) Siu Ling Wong et al.   FASEB JOURNAL

Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis

(2018) Dirk J. van der Windt et al.   HEPATOLOGY

Neutrophil peptidyl arginine deiminase-4 has a pivotal role in ischemia/reperfusion-induced acute kidney injury

(2018) Wesley M. Raup-Konsavage et al.   KIDNEY INTERNATIONAL

Citrullination of RGG Motifs in FET Proteins by PAD4 Regulates Protein Aggregation and ALS Susceptibility

(2018) Chizu Tanikawa et al.   Cell Reports

PADI4 Stimulates Esophageal Squamous Cell Carcinoma Tumor Growth and Up-regulates CA9 Expression

(2018) Chunyan Liu et al.   MOLECULAR CARCINOGENESIS

Peptidylarginine deiminase-4 gene polymorphisms are associated with systemic lupus erythematosus and lupus nephritis

(2018) L Massarenti et al.   SCANDINAVIAN JOURNAL OF RHEUMATOLOGY

Synthesis and Biological Evaluation of an Indazole-Based Selective Protein Arginine Deiminase 4 (PAD4) Inhibitor

(2018) Caroline Chandra Tjin et al.   ACS Medicinal Chemistry Letters

Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular Trap Inhibition

(2018) Hui Wang et al.   Scientific Reports

Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils

(2018) Yebin Zhou et al.   Scientific Reports

Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix

(2018) A. E. Yuzhalin et al.   Nature Communications

PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis

(2017) Sindhu Koushik et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

PAD4 Deficiency Decreases Inflammation and Susceptibility to Pregnancy Loss in a Mouse Model

(2016) L. Erpenbeck et al.   BIOLOGY OF REPRODUCTION

Neutrophil extracellular traps — the dark side of neutrophils

(2016) Ole E. Sørensen et al.   JOURNAL OF CLINICAL INVESTIGATION

Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition

(2016) QIONG DUAN et al.   ONCOLOGY REPORTS

Abrogation of collagen-induced arthritis by a peptidyl arginine deiminase inhibitor is associated with modulation of T cell-mediated immune responses

(2016) Joanna Kawalkowska et al.   Scientific Reports

At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases

(2015) April Barnado et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Design, Synthesis, and Biological Evaluation of Tetrazole Analogs of Cl-Amidine as Protein Arginine Deiminase Inhibitors

(2015) Venkataraman Subramanian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation

(2015) Huw D Lewis et al.   Nature Chemical Biology

Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis

(2015) A. Warnatsch et al.   SCIENCE

A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells

(2015) Guanhua Song et al.   Oncotarget

Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model

(2015) Yu Seri et al.   Scientific Reports

The W620 Polymorphism in PTPN22 Disrupts Its Interaction With Peptidylarginine Deiminase Type 4 and Enhances Citrullination and NETosis

(2015) Hui-Hsin Chang et al.   Arthritis & Rheumatology

Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lprmice

(2014) Jason S Knight et al.   ANNALS OF THE RHEUMATIC DISEASES

Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2

(2014) Carmelo Carmona-Rivera et al.   ANNALS OF THE RHEUMATIC DISEASES

A novel role for protein arginine deiminase 4 in pluripotency: The emerging role of citrullinated histone H1 in cellular programming

(2014) Daniel J. Slade et al.   BIOESSAYS

Citrullination and Proteolytic Processing of Chemokines by Porphyromonas gingivalis

(2014) E. A. V. Moelants et al.   INFECTION AND IMMUNITY

Citrullination unravels stem cells

(2014) Daniel J Slade et al.   Nature Chemical Biology

Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation

(2014) Rachel Deplus et al.   NUCLEIC ACIDS RESEARCH

Peptidylarginine deiminase IV promotes the development of chemoresistance through inducing autophagy in hepatocellular carcinoma

(2014) Tingting Fan et al.   Cell and Bioscience

Neutrophil Extracellular Trap-Derived Enzymes Oxidize High-Density Lipoprotein: An Additional Proatherogenic Mechanism in Systemic Lupus Erythematosus

(2014) Carolyne K. Smith et al.   Arthritis & Rheumatology

Thrombosis: tangled up in NETs

(2013) K. Martinod et al.   BLOOD

miR-155: an ancient regulator of the immune system

(2013) Elena Vigorito et al.   IMMUNOLOGICAL REVIEWS

Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus

(2013) Jason S. Knight et al.   JOURNAL OF CLINICAL INVESTIGATION

Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis

(2013) Jonathan Cools-Lartigue et al.   JOURNAL OF CLINICAL INVESTIGATION

Novel Inhibitors of Protein Arginine Deiminase with Potential Activity in Multiple Sclerosis Animal Model

(2013) Lianhu Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dysregulation of PAD4-mediated citrullination of nuclear GSK3  activates TGF-  signaling and induces epithelial-to-mesenchymal transition in breast cancer cells

(2013) S. C. Stadler et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Decreased PADI4 mRNA Association with Global Hypomethylation in Hepatocellular Carcinoma During HBV Exposure

(2012) Changsong Zhang et al.   CELL BIOCHEMISTRY AND BIOPHYSICS

Neuronal PAD4 expression and protein citrullination: Possible role in production of autoantibodies associated with neurodegenerative disease

(2012) Nimish K. Acharya et al.   JOURNAL OF AUTOIMMUNITY

Anticancer Peptidylarginine Deiminase (PAD) Inhibitors Regulate the Autophagy Flux and the Mammalian Target of Rapamycin Complex 1 Activity

(2012) Yuji Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Molecular Pathology of Alzheimer's Disease

(2012) Charles R. Harrington   NEUROIMAGING CLINICS OF NORTH AMERICA

Role of peptidylarginine deiminase 4 (PAD4) in pig parthenogenetic preimplantation embryonic development

(2012) Manjula Brahmajosyula et al.   ZYGOTE

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

(2012) Chizu Tanikawa et al.   Nature Communications

Synthesis and Screening of a Haloacetamidine Containing Library To Identify PAD4 Selective Inhibitors

(2011) Justin E. Jones et al.   ACS Chemical Biology

Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor

(2011) Alexander A. Chumanevich et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Peptidylarginine Deiminases Present in the Airways during Tobacco Smoking and Inflammation Can Citrullinate the Host Defense Peptide LL-37, Resulting in Altered Activities

(2011) Ola Kilsgård et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Citrullination of Inhibitor of Growth 4 (ING4) by Peptidylarginine Deminase 4 (PAD4) Disrupts the Interaction between ING4 and p53

(2011) Qin Guo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Elevated miR-155 Promotes Inflammation in Cystic Fibrosis by Driving Hyperexpression of Interleukin-8

(2011) Sharmistha Bhattacharyya et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

N-α-Benzoyl-N5-(2-Chloro-1-Iminoethyl)-l-Ornithine Amide, a Protein Arginine Deiminase Inhibitor, Reduces the Severity of Murine Collagen-Induced Arthritis

(2011) Van C. Willis et al.   JOURNAL OF IMMUNOLOGY

Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues, and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus

(2011) E. Villanueva et al.   JOURNAL OF IMMUNOLOGY

Rac2 is required for the formation of neutrophil extracellular traps

(2011) Michael Byung H. Lim et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Discovery of peptidylarginine deiminase-4 substrates by protein array: antagonistic citrullination and methylation of human ribosomal protein S2

(2011) Qin Guo et al.   Molecular BioSystems

Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus

(2011) G. S. Garcia-Romo et al.   Science Translational Medicine

Localization and expression of peptidylarginine deiminase 4 (PAD4) in mammalian oocytes and preimplantation embryos

(2011) Manjula Brahmajosyula et al.   ZYGOTE

A fluopol-ABPP HTS assay to identify PAD inhibitors

(2010) Bryan Knuckley et al.   CHEMICAL COMMUNICATIONS

The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1)

(2010) Rocio T. Martinez-Nunez et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps

(2010) Venizelos Papayannopoulos et al.   JOURNAL OF CELL BIOLOGY

Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases

(2010) Steffen Massberg et al.   NATURE MEDICINE

Coordination of PAD4 and HDAC2 in the regulation of p53-target gene expression

(2010) P Li et al.   ONCOGENE

Anti-cyclic citrullinated peptide antibody (anti-CCP antibody) is present in the sera of patients with dementia of Alzheimer’s type in Asian

(2009) K. Satoh et al.   ACTA NEUROLOGICA SCANDINAVICA

Regulation of Protein Citrullination through p53/PADI4 Network in DNA Damage Response

(2009) C. Tanikawa et al.   CANCER RESEARCH

Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation

(2009) Yanming Wang et al.   JOURNAL OF CELL BIOLOGY

Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-  blocking agents

(2008) E H Halvorsen et al.   ANNALS OF THE RHEUMATIC DISEASES

Histone Arg Modifications and p53 Regulate the Expression ofOKL38, a Mediator of Apoptosis

(2008) Hongjie Yao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation

(2008) Paul Proost et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Regulation of p53 Target Gene Expression by Peptidylarginine Deiminase 4

(2008) P. Li et al.   MOLECULAR AND CELLULAR BIOLOGY

Regulation of chemokine activity by posttranslational modification

(2008) A MORTIER et al.   PHARMACOLOGY & THERAPEUTICS

Profiling Protein Arginine Deiminase 4 (PAD4): A novel screen to identify PAD4 inhibitors

(2007) Bryan Knuckley et al.   BIOORGANIC & MEDICINAL CHEMISTRY