Investigators at The Scripps Research Institute have successfully used a drug-discovery technique based on sequence data to identify a small molecule that selectively targets a microRNA associated with cancer.

Researchers at The Scripps Research Institute's (TSRI) Jupiter, FL, campus have successfully used a drug-discovery technique based on human sequence data to identify a lead drug compound that selectively targets RNA associated with cancer.

“For the first time, we've been able to take the products of genetic material and, in a rational way, design small molecules that precisely target a cancer-associated microRNA,” says Matthew Disney, PhD, associate professor at TSRI and lead author of the study, reported online in February (Nat Chem Biol 2014;10:291–7).

Disney's team developed a technique, dubbed Inforna, to identify therapeutic small molecules based on RNA sequence information. Then, in the current study, they screened millions of potential precursor microRNA–drug interactions and designed 27 compounds that target disease-associated microRNAs.

The most active interaction was between the compound benzimidazole, which has antiparasitic and antifungal properties, and microRNA-96, which represses the forkhead family transcription factor FOXO1, inhibits apoptosis, and is associated with metastatic breast cancer, Disney says. Benzimidazole upregulated FOXO1 in cancer cells and induced apoptosis.

“The selectivity of the small molecule was very surprising to us,” says Disney. “Known chemotherapy drugs like cisplatin [Platinol-AQ; Bristol-Myers Squibb] and chlorambucil [Leukeran; Aspen Global] often act indiscriminately on healthy and diseased cells and don't target biomolecules specific to cancer, whereas this molecule appeared to be very selective for a microRNA that is contributing to cancer.”

The next step for researchers is testing the efficacy of microRNA-targeting compounds in animal models, Disney says.

The current method of targeting microRNAs is to use oligonucleotides, which generally are not cell permeable and may cause nonspecific immune effects, says Disney. The Inforna technique may allow identification of small-molecule lead compounds that specifically target disease-associated RNAs without the disadvantages of oligonucleotides.

The Inforna technique has far-reaching implications, Disney says, and could lead to new drugs targeting any disease-associated RNA molecule.

“In the case of a hepatitis or human immunodeficiency virus that's resistant to chemotherapeutics, potentially you could use Inforna to design small molecules that specifically target and modulate mutated viral RNAs to be a potential therapy,” he explains.

“We're trying to broadly use this as a technological platform where one could target any RNA from sequence,” he continues. “That could allow us to make a chemical probe to help study the function of these RNAs.”

For more news on cancer research, visit Cancer Discovery online at