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NCCU BRITE Lab Licenses Chemical Compound for Research

John E. Scott
Alfred L. Williams

Discovery of a molecule that could make chemotherapy treatments more tolerable for some patients has resulted in the first commercial license executed by the Biomanufacturing Research Institute and Technology Enterprise (BRITE) at North Carolina Central University.

Parnassus Medical Systems of Houston, Texas, licensed the molecule from the chemical compound library that is housed at BRITE. University researchers Alfred L. Williams, Ph.D., and John E. Scott, Ph.D., both associate professors of pharmaceutical sciences at NCCU, discovered the ability of a particular small molecule compound to inhibit a bacterial enzyme causing severe diarrhea in some cancer patients.

“With certain cancer treatments, chemotherapy becomes dose-limiting due to the side effect of diarrhea. Our researchers were able to identify the small molecule compound that limits that response, potentially allowing more patients to benefit from the treatment,” said Undi Hoffler, Ph.D., who is interim vice chancellor for Research and Economic Development at NCCU. 

The BRITE library consists of 350,000 compounds donated by Biogen Idec in 2006 and is one the largest publically owned compound libraries in the region. The compounds are used in drug-discovery research at BRITE and the university’s Julius L. Chambers Biomedical/Biotechnology Research Institute.

Because the compound is unique to the compound library at NCCU, the university was able to receive a patent for its use. Parnassus Medical Systems, which works to develop drugs for cancer, neurological disorders and other diseases, licensed the patent in early 2016. Scott called the event a “milestone” for the university.

“It’s the first patent that BRITE has licensed, and it demonstrates the value of our high-throughput screening core facility here as well as the compound collection we have,” Scott said.

The researchers collaborated on the study with Matt Redinbo, Ph.D., co-inventor and professor at the University North Carolina at Chapel Hill who uses the bacterial enzyme beta-glucuronidase in his research.

Camptosar, an effective chemotherapy for colon and rectal cancer, should become non-toxic in the body and eliminated through the intestine. However, the beta-glucuronidase enzyme, which is normally present in the intestines, converts the drug back into a toxic form that damages the intestinal wall and triggers diarrhea.

The diarrhea, occurring five or more days after treatment, can be severe enough to be life-threatening and results in treatment delays, reduction in dosage or abandonment of future treatments. A drug that inhibits the activity of this bacterial enzyme may prevent this severe diarrhea and may allow increased doses of this chemotherapy.

Using high-throughput screening, an automated process to quickly assay a large number of compounds, the researchers tested more than 30,000 chemicals to find the single molecule with the greatest potential to inhibit the enzyme’s activity.

“We developed the chemistry to synthesize the molecule and make analogs to study their structural activity relationships,” Williams said. “This compound was identified as an inhibitor of that enzyme.”

What happens next with the discovery is up to the licensee.

“They may either try to develop the compound further or see if there are any other companies interested in using the compound,” Williams said.

Published: Tuesday, July 19, 2016
by Senior Writer and Editor, Renee Elder
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