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

Nat Chem Biol

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.); University of Massachussetts Medical School, Worcester, Massachusetts, USA (P.R.T.).

Published: March 2015

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397581PMC
http://dx.doi.org/10.1038/nchembio.1735DOI Listing

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