Recycled and reused: scientists develop a library to help teach old drugs new tricks.
Maryam Mahdi |
In sunny San Diego lies a library of drugs, which researchers are encouraging companies to exploit to repurpose old drugs for new needs. The open access drug catalog, ReFRAME, consists almost entirely of small molecules – all of which have reached the clinical development stage or undergone thorough preclinical filing – and is already showing results. Two compounds from the library have been identified as suitable treatments for tuberculosis and Cryptosporidium spp (1).
ReFRAME was developed by researchers at Calibr, a non-profit arm of Scripps Research, by drawing on databases from Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects. The size of the collection makes it conducive to medium-throughput assays and eliminates the need for drawn out assay optimization. “We have 12,000 compounds, of which 6000 are commercially available,” says Arnab Chatterjee, Vice President of Medical Chemistry at Calibr. “The size of the collection makes it conducive to medium-throughput assays and eliminates the need for drawn out assay optimization.”
Chatterjee is particularly excited about the potential of the library to be used in the fight against neglected diseases. ReFRAME can be used to identify potential drug candidates by introducing compounds to disease-causing microorganisms. In the field of rare and neglected diseases, there is often less commercial motivation for research and development but the Calibr researchers hope that ReFRAME can be used to cut costs and timelines. Successful drug repurposing depends on the ability to translate in vitro data to proof of concept so having molecules that have already progressed to trials is a huge advantage. The Calibr team believe that it should be possible to take a screen to a clinical trial in less than 6 months.
To highlight the potential of the drug library, Chatterjee and colleagues focused on TB and Cryptosporidium spp. Cryptosporidium is a parasite which causes cryptosporidiosis, a diarrheal disease, and a leading cause of death in children worldwide. Only one drug is available for treatment and the cost benefit of its use are questionable due to the negative effects the drug is known to have.
“The ReFRAME technology has given the scientists at Calibr the opportunity to find new compounds and make a difference to the treatment of disease,” says Chatterjee. “We hope others will also take advantage of this library. Many people simply don’t have the tools or resources to find new therapeutics. We can have the most impact by sharing our data and we’re extremely excited about that!”
An open-access data portal (https://reframedb.org) has also been developed to share screen hits to encourage additional follow-up.
- J Janes et al., “The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis,” PNAS 115, 10750-10755 (2018).