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

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2015

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Lewis, H. D., J. Liddle, J. E. Coote, S. J. Atkinson, M. D. Barker, B. D. Bax, K. L. Bicker, et al. 2015. “Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.” Nature chemical biology 11 (3): 189-191. doi:10.1038/nchembio.1735. http://dx.doi.org/10.1038/nchembio.1735.

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PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases, through clinical genetics and gene disruption in mice. Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD4 enzyme have, for the first time, validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation. The therapeutic potential of PAD4 inhibitors can now be explored.

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