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Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.
Lewis, Huw D; Liddle, John; Coote, Jim E; Atkinson, Stephen J; Barker, Michael D; Bax, Benjamin D; Bicker, Kevin L; Bingham, Ryan P; Campbell, Matthew; Chen, Yu Hua; Chung, Chun-Wa; Craggs, Peter D; Davis, Rob P; Eberhard, Dirk; Joberty, Gerard; Lind, Kenneth E; Locke, Kelly; Maller, Claire; Martinod, Kimberly; Patten, Chris; Polyakova, Oxana; Rise, Cecil E; Rüdiger, Martin; Sheppard, Robert J; Slade, Daniel J; Thomas, Pamela; Thorpe, Jim; Yao, Gang; Drewes, Gerard; Wagner, Denisa D; Thompson, Paul R; Prinjha, Rab K; Wilson, David M.
Affiliation
  • Lewis HD; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Liddle J; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Coote JE; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Atkinson SJ; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Barker MD; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Bax BD; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Bicker KL; Department of Chemistry, Scripps Florida, The Scripps Research Institute, Jupiter, Florida, USA.
  • Bingham RP; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Campbell M; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Chen YH; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Chung CW; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Craggs PD; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Davis RP; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Eberhard D; Cellzome GmbH, a GSK company, Heidelberg, Germany.
  • Joberty G; Cellzome GmbH, a GSK company, Heidelberg, Germany.
  • Lind KE; ELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
  • Locke K; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Maller C; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Martinod K; 1] 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.
  • Patten C; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Polyakova O; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Rise CE; ELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
  • Rüdiger M; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Sheppard RJ; 1] 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.
  • Slade DJ; 1] 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 Massac
  • Thomas P; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Thorpe J; Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Yao G; ELT Boston, Platform Technology and Science, GlaxoSmithKline, Waltham, Massachusetts, USA.
  • Drewes G; Cellzome GmbH, a GSK company, Heidelberg, Germany.
  • Wagner DD; 1] 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.
  • Thompson PR; 1] 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 Massac
  • Prinjha RK; EpiNova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline,Medicines Research Centre, Stevenage, Hertfordshire, UK.
  • Wilson DM; 1] 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.
Nat Chem Biol ; 11(3): 189-91, 2015 Mar.
Article in En | MEDLINE | ID: mdl-25622091
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Benzimidazoles / Enzyme Inhibitors / Hydrolases / Neutrophils Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Nat Chem Biol Journal subject: BIOLOGIA / QUIMICA Year: 2015 Type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Benzimidazoles / Enzyme Inhibitors / Hydrolases / Neutrophils Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Nat Chem Biol Journal subject: BIOLOGIA / QUIMICA Year: 2015 Type: Article Affiliation country: United kingdom