New ReFRAME drug repurposing collection offers hope for treating major diseases

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The Calibr scientists are using this collection, called ReFRAME, to identify existing drugs that show promise for treating major diseases. Because of this ReFRAME initiative, two FDA-approved drugs are already being tested in clinical trials--one as a treatment for tuberculosis and another for the parasite Cryptosporidium spp., a major cause of severe diarrhea--within only a few short years of Calibr scientists discovering their utility. This contrasts with the much longer timelines that often hinder new drug development.

To construct ReFRAME, Calibr researchers gathered data on more than 12,000 small-molecule drugs by combining three widely-used commercial drug databases (Clarivate Integrity, GVK Excelra GoStar and Citeline Pharmaprojects), which are typically used by pharmaceutical and biotech companies to assess competition and guide drug research and development.

"ReFRAME was developed as a singular new resource for the global health drug discovery community and is the largest and most comprehensive repurposing collection available," says Arnab Chatterjee, PhD, vice president of medicinal chemistry at Calibr and lead researcher on the project. "In addition to consolidating compounds from multiple existing collections, we synthesized around 5,000 molecules that are not commercially available--from which we identified the two new hits against Cryptosporidium."

In their study, the Calibr scientists placed the parasites in thousands of small chambers and dosed them with samples of the drugs to determine which compounds killed them. Drugs that killed Cryptosporidium in the chambers were then given to mice infected with the parasite, and two drugs, VB-201(CI-201) and ASP-7962, proved effective at treating the infections in the animals. The researchers were able to move from identifying the compounds to animal studies in about two months, a remarkably rapid advance from one phase of drug discovery research to another.

"These two compounds show promise for providing therapeutics for targeting the parasite and not just the symptoms," says Case McNamara, PhD, a principal investigator at Calibr and coauthor on the paper. "If they prove effective at treating this disease in humans, it could impact the lives of millions of people worldwide."

Source: NEWS Medical Lifesciences