Researchers at the National Institutes of Health's Chemical Genomics Center have launched a comprehensive catalog of all drugs approved for human or veterinary use, as well as informatics and screening resources, with an eye toward accelerating drug repurposing research.
While drug repurposing has historically been the result of serendipitous clinical observations, NCGC Director Christopher Austin says that his group's primary motivation for creating the NCGC Pharmaceutical Collection — or NPC — was to enable rational repurposing efforts. The team is also interested in the chemical genomics and toxicology aspects of the project, Austin says, adding that he expects the NCGC to issue solicitations for NPC-centric projects this summer.
"We wanted a collection of compounds that would give us as much information as we could possibly get about the many mechanisms of action — that is, different ways that these compounds can work, both for beneficial purposes and for adverse event purposes — in order to understand all of the different pharmacologies that these compounds can do," Austin says. "If we can understand that, our hypothesis was, and is, that we would be able to produce better drugs that have fewer side effects."
Though several other teams have previously attempted similar efforts, Austin says that most fell victim to the idiosyncrasies of regulatory record-keeping, and thus generated skewed results. "What we found was that a lot of the previous estimates which had taken these data, understandably, at face value had actually both double-counted, or multiply counted, the same drug or had done the opposite and missed things completely," he says.
In an April Science Translational Medicine paper, Austin and his colleagues chart the nearly five-year-long course of their efforts to generate complete and non-redundant lists of all drugs approved for human or veterinary use worldwide as well as thousands of registered investigational compounds that are not approved for use; to begin acquiring physical samples for each worldwide-approved compound; and to build the informatics and screening resources. All told, the collection includes 2,356 compounds approved by the US Food and Drug Administration for human use; 3,936 approved worldwide for human use; and 4,935 compounds that are registered for experimental human use, though not approved by any regulatory agency. So far, Austin says, his team has acquired around 1,300 physical samples for its screening resource. "On the procurement side, simply getting the drugs was a real challenge," he adds.
Beyond repurposing activities, researchers are also currently using the NPC compounds to gain an improved toxicological understanding of each, and to establish the characteristics of small-molecule compounds that confer biological activity. Researchers at the NCGC have screened NPC compounds against more than 200 target and pathway assays. In addition, Austin says the entire catalog will be incorporated into the more than 11,000 compounds that will be screened as part of the National Toxicology Program's Tox21 initiative.
Austin says that on the screening side, his team intends to continue to build its physical collection. "On the informatics side — and we're really excited about this — the growth is going to be in further annotating the compounds that are there: to add further data on pathways, other diseases, on symptoms of these diseases, organ systems that are affected by these diseases and — we hope — data on the investigational drugs," he says.