LA JOLLA, Calif. — You could easily mistake it for a big CD rack.
Inside the lab at the California Institute of Biomedical Research, known as Calibr, sits a stacked array of several dozen plastic microplates. These rectangular cartridges have hundreds of wells on their surface that act as mini test tubes — and hold almost all the small-molecule drugs that have been approved by the Food and Drug Administration or tested in clinical trials.
Dubbed the “ReFRAME” library, this collection of over 12,000 drug compounds — the largest of its kind ever assembled — is sourced by Calibr researchers to try to find new uses for existing drugs.
Here’s how it works: First, researchers identify an illness in need of more treatment options. Then robots rapidly dose samples of a disease-causing pathogen with the entire ReFRAME collection. If one of the drugs is shown to be effective against the sample, the researchers have a “hit.”
One of Calibr’s first hits was on the parasite Cryptosporidium. Cryptosporidiosis causes severe diarrhea and is a leading killer of children in developing countries. The drug nitazoxanide, the only existing approved treatment for the condition, is only marginally effective. Using the ReFRAME library, Calibr researchers discovered that the leprosy drug clofazimine could also be used to treat cryptosporidiosis. It is currently in clinical trials in Malawi.
“The idea is that really we can dramatically reduce the amount of time it takes to go from a basic discovery to actually testing something in humans,” said Arnab Chatterjee, Calibr’s vice president of medicinal chemistry. “The real critical and difficult element of even in small-molecule drug discovery is that the ability to go from an interesting hit to a molecule you can actually safely test in humans can take anywhere from four to six years. [By using ReFRAME], you can actually go from a screen to a clinical trial in a matter of six months.”
Calibr, a nonprofit, is making its collection, and results from its research, available to scientists worldwide. Chatterjee hopes this will allow researchers to find new treatments for neglected tropical diseases.
“That’s really where we would love for this collection to have major impact.”
Correction: An earlier version of this story misstated Arnab Chatterjee’s title.