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  • Title: Proteolytic assay-based screening identifies a potent inhibitor of anthrax lethal factor.
    Author: Park HC, Sung SR, Lim SM, Lee JS, Kim SK, Yoon MY.
    Journal: Microb Pathog; 2012 Aug; 53(2):109-12. PubMed ID: 22561400.
    Abstract:
    Anthrax lethal factor (LF), a Zn(2+)-dependent metalloprotease, is a key virulence component of anthrax toxin. Here, we used proteolytic assay-based screening to identify novel LF inhibitors from a naturally extracted chemical library. The screening identified four compounds that inhibited in vitro proteolytic activity of LF with an IC(50) of low micromolar range (11-20 μM). Three of these compounds were toxic to the mouse macrophage-like cell line, RAW 264.7. Compound 200 was non-toxic, however, and successfully protected Raw 264.7 cells from a lethal toxin challenge with an IC(50) of 39.2 μM. We also identified possible binding modes of compound 200 by molecular docking.
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