A high-throughput screening approach to anthrax lethal factor inhibition

作者：Johnson Sherida L; Chen Li Hsing; Pellecchia Maurizio^*

来源：Bioorganic Chemistry, 2007, 35(4): 306-312.

DOI：10.1016/j.bioorg.2006.12.005

• anthrax
• lethal factor
• high-throughput screening
• Botulinum Neurotoxin

A high-throughput screening approach was used to identify new inhibitors of the metallo-protease lethal factor from Bacillus anthracis. A library of similar to 14,000 compounds was screened using a fluorescence-based in vitro assay and hits were further characterized enzymatically via measurements of IC50 and K-i 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.

• 出版日期2007-8
• 单位河北医科大学