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ID: ALA1152503

Journal: Bioorg Med Chem

Title: Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death.

Authors: Zhu PJ, Hobson JP, Southall N, Qiu C, Thomas CJ, Lu J, Inglese J, Zheng W, Leppla SH, Bugge TH, Austin CP, Liu S.

Abstract: Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a beta-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization.

CiteXplore: 19540764

DOI: 10.1016/j.bmc.2009.05.054