New screening method turns up potential compound for treating anthrax

University of Chicago scientists have identified a compound that halts the activity of a deadly toxin called anthrax lethal factor in laboratory tests. Nature Biotechnology will publish the findings online on May 16 and in the June issue of the journal's print edition.

Anthrax lethal factor can only be effectively treated with antibiotics if administered soon after infection, making it difficult to treat patients who were unknowingly exposed to the bacterium. The Chicago research aims to develop a drug that could treat anthrax after antibiotics become ineffective.

The Chicago team discovered that a compound called DS-998 showed promising activity against anthrax lethal factor in cell cultures. Lethal factor is a molecule that chops up and renders inactive a protein that helps cells stay healthy. DS-998 blocks lethal factor's harmful cutting action.

The Chicago research is also the first time application of mass spectrometry to screen a library of compounds for medical applications. "We screened 10,000 compounds in three days. We estimate that it would be possible to screen 50,000 compounds a day with available robotic equipment," said Milan Mrksich, Professor in Chemistry at the University of Chicago. His co-authors of the Nature Biotechnology article are Dal-Hee Min, a Ph.D. student in chemistry, and Wei-Jen Tang, Associate Professor in the Ben May Institute for Cancer Research, both at the University of Chicago,

Rapid screening is an important component in making drug development more economical. It can cost a pharmaceutical company $250 million to develop a drug. Research and development alone can exceed $25 million, Mrksich said. "Typically hundreds of thousands of molecules are screened to identify 10 that are candidate drug leads," he said.

The search focused on small-molecule compounds. "In order to prevent the action of these toxins you need to have a molecule that is easily penetrable into the cell

Contact: Steve Koppes
University of Chicago

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