Because of the need for an oxygen-free environment, most tests on amoebas are conducted in small batches, testing one or two compounds at a time. The modern approach to these tests conducting thousands of screens at once had never been done in an anaerobic environment. So Debnath reached out to the UCSF Small Molecule Discovery Center in the UCSF School of Pharmacy and QB3, which uses technology from the pharmaceutical industry to help bioscience researchers screen the targets they discover against potential therapies. Together, they modified the standard screen so it could be used in an anaerobic environment.
The second lucky stroke was a call McKerrow received during the project from Iconix Biosciences, a Menlo Park, CA, company that was going out of business. Iconix offered the Sandler Center its screening library of 900 compounds each in its own vial that have been approved by the FDA for human use.
With more than half of the FDA-approved compounds at their disposal, the team worked with the Small Molecule Discovery Center to screen the drugs against amoebas.
The results were startling: The drug was 10 times more potent in the screens against E. histolytica than the current treatment.
"The top hit was this drug auranofin, which caught our attention for a couple of reasons," McKerrow said. "First, it was more effective than the current drug, and importantly, it was a drug that has been given to people since 1985. So we knew it could be taken orally and was safer than the current drug for amoebas."
Beyond the Lab
Thus, they knew they had a safe drug that was effectiv
|Contact: Kristen Bole|
University of California - San Francisco