Scientists have identified a compound that halts the activity of a deadly toxin called anthrax lethal factor.
University of Chicago scientists have identified a compound that halts the activity of a deadly toxin called anthrax lethal factor through laboratory tests.
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. They 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 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.
Rapid screening is an important component in making drug development more economical. It can cost a pharmaceutical company 250 million dollars to develop a drug and research and development alone can exceed 25 million dollars. "Typically hundreds of thousands of molecules are screened to identify 10 that are candidate drug leads," said Mrksich.
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," said Wei-Jen Tang, the study's co-author.
Tang said that DS-998 compound could one day lead to the development of a new drug for the treatment of anthrax but he also cautioned that research remains in the early stages.
"Discovering proteins that have roles in diseases processes is the first step in the drug discovery process, but still a very long way from the actual development of a drug," added Mrksich.
Mass spectrometry is widely used to identify proteins in biological studies, but until now the technique has required specialized training. It has great potential for application to university research programs, which originate many drug targets.
"By having the screening facility on campus, it's possible to see basic research take one important step further toward a drug discovery development program," Mrksich said.