title: A high-throughput screening approach to anthrax lethal factor inhibition.
abstract: A high-throughput screening approach was used to identify new inhibitors of the metallo-protease lethal factor from Bacillus anthracis. A library of approximately 14,000 compounds was screened using a fluorescence-based in vitro assay and hits were further characterized enzymatically via measurements of IC50 and Ki values against a small panel of metallo-proteases. This study led to the identification of new scaffolds that inhibit LF and the Botulinum Neurotoxin Type A in the low micromolar range, while sparing the human metallo-proteases MMP-2 and MMP-9. Therefore, these scaffolds could be further exploited for the development of potent and selective anti-toxin agents.
authors.affiliation: Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Sherida L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Li-Hsing
authors.initials: LH
authors.lastname: Chen
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D045726:Metalloproteases / Q000037:antagonists & inhibitors; D015394:Molecular Structure
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C030325:anthrax toxin; D045726:Metalloproteases