ArticleNature chemical biology2015
Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.
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Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 476 papers, 1 of them a synthesis that pooled it.
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476citing papers in PubMed, 1 pooled it
20.1field-weighted citation impact, top 1% of its field
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Who cites it
476 citing papers in PubMed, 1 synthesis or guideline pooled it, 735 citations in OpenAlex.
- From immunological mechanisms to targeted therapies: a bibliometric analysis in the domain of research concerning neutrophil extracellular traps and pulmonary diseases (2006-2025).Frontiers in immunology · 2026Pooled it
- Review
- Review
- DVT-primed neutrophils reshape the brain microenvironment to promote brain metastasis.bioRxiv : the preprint server for biology · 2026Article
- PAD4-DB: A Curated Structure-Activity Resource Reveals Hub-Organized Activity Cliffs and Scaffold-Dependent SAR Ruggedness in PAD4 Inhibitors.International journal of molecular sciences · 2026Article
- Review
- A human PBMC-based new approach method reveals PFAS-driven T-cell proliferation and immune dysregulation.Archives of toxicology · 2026Article
- Dual Targeting of Net Formation and Coagulation Improves Survival and Organ Protection in Experimental Sepsis.Shock (Augusta, Ga.) · 2026Article
- Multi-Omics Profiling Reveals Neutrophil Extracellular Trap Dysregulation in Diabetic Foot Ulcer Healing Impairment.International journal of molecular sciences · 2026Article
- PAD4-generated citrullinated histones are triggers for autoinflammation in cryopyrin-associated periodic syndrome.Cell death and differentiation · 2026Article
- Review
- A 'Tangled Web' in the CNS: unraveling neutrophil extracellular traps in neurological disorders.Molecular neurodegeneration · 2026Review
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- CSF2 drives radiation-induced lung injury by eliciting PADI4-high pathogenic neutrophils.Journal of translational medicine · 2026Article
- Dual roles of neutrophil extracellular traps in tumors: From pro-metastatic mechanisms to immunotherapeutic strategies (Review).Oncology letters · 2026Review
- Review
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Regulated cell death in sepsis: reframing NETosis within the spectrum of apoptosis and inflammatory lytic death.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
416 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 4 institutions in 2 countries.
Huw D LewisEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
John LiddleEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Jim E CooteMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Stephen J AtkinsonEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Michael D BarkerEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Benjamin D BaxMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Kevin L BickerDepartment of Chemistry, Scripps Florida, The Scripps Research Institute, Jupiter, Florida, USA.
Ryan P BinghamMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Matthew CampbellEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Yu Hua ChenMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Chun-Wa ChungMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Peter D CraggsMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Rob P DavisEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Dirk EberhardCellzome GmbH, a GSK company, Heidelberg, Germany.
Gerard JobertyCellzome GmbH, a GSK company, Heidelberg, Germany.
Kenneth E LindELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
Kelly LockeMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Claire MallerEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Kimberly Martinod1] Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Immunology Graduate Program, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
Chris PattenEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
Oxana PolyakovaMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Cecil E RiseELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
Martin RüdigerMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Robert J Sheppard1] EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK. [2] AstraZeneca, Oncology iMed, Cambridge Science Park, Cambridge, UK (R.J.S. and D.M.W.); Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA (D.J.S.); University of Massachussetts Medical School, Worcester, Massachusetts, USA (P.R.T.).
Daniel J Slade1] Department of Chemistry, Scripps Florida, The Scripps Research Institute, Jupiter, Florida, USA. [2] AstraZeneca, Oncology iMed, Cambridge Science Park, Cambridge, UK (R.J.S. and D.M.W.); Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA (D.J.S.); University of Massachussetts Medical School, Worcester, Massachusetts, USA (P.R.T.).
Pamela ThomasMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Jim ThorpeMolecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Gang YaoELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
Gerard DrewesCellzome GmbH, a GSK company, Heidelberg, Germany.
Denisa D Wagner1] Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA. [3] Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
Paul R Thompson1] Department of Chemistry, Scripps Florida, The Scripps Research Institute, Jupiter, Florida, USA. [2] AstraZeneca, Oncology iMed, Cambridge Science Park, Cambridge, UK (R.J.S. and D.M.W.); Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA (D.J.S.); University of Massachussetts Medical School, Worcester, Massachusetts, USA (P.R.T.).
Rab K PrinjhaEpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
David M Wilson1] EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK. [2] AstraZeneca, Oncology iMed, Cambridge Science Park, Cambridge, UK (R.J.S. and D.M.W.); Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA (D.J.S.); University of Massachussetts Medical School, Worcester, Massachusetts, USA (P.R.T.).
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USScripps Research Institute · USBoston Children's Hospital · US
Funding
TRANSFUSION BIOLOGY AND MEDICINET32HL066987 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI JOHN P MANIS · 2001 to 2026
$10.2MHaloacetamidine based inactivators of Protein Arginine Deiminase 4R01GM079357 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI THOMPSON, PAUL R · 2007 to 2016
$3.3MPlatelet adhesion to neutrophil extracellular DNA traps: role in thrombosisR01HL102101 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI WAGNER, DENISA D · 2011 to 2016
$2.7MNHLBI NIH HHS R01 HL102101NHLBI NIH HHS T32 HL066987NIGMS NIH HHS GM079357NIGMS NIH HHS R01 GM079357
Abstract
PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.
Indexed as
AnimalsBenzimidazolesBinding, CompetitiveCalciumCitrullineEnzyme InhibitorsHEK293 CellsHistonesHumansHydrolasesIn Vitro TechniquesMiceModels, MolecularNeutrophilsProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4BenzimidazolesCalciumCitrullineEnzyme InhibitorsGSK199HistonesHydrolasesPADI4 protein, humanpeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Small Molecule Libraries
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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.