Troy, N.Y. — Seeking to improve and accelerate drug discovery, researchers at Rensselaer Polytechnic Institute and University of California at Berkeley have developed a new technique to rapidly analyze the toxicity of compounds at early stages in the drug discovery process.

The researchers designed a new technique that uses a human enzyme chip called the MetaChip, or metabolizing enzyme toxicology assay chip.

“The MetaChip offers a new approach in the identification of pharmacologically safe and effective lead drug compounds for advancement to the preclinical phase of drug development,” said Jonathan Dordick, the Howard P. Isermann ‘42 Professor of Chemical and Biological Engineering at Rensselaer. “The research results thus far indicate that this technique could be incorporated into an effective process for toxicity analysis at early stages in drug discovery.”

The research findings are reported today in the Proceedings of the National Academy of Sciences Online Early Edition in a paper titled “Metabolizing Enzyme Toxicology Assay Chip (MetaChip) for High-Throughput Microscale Toxicity Analyses.” The paper will be printed in the Jan. 25 issue of Proceedings of the National Academy of Sciences.

Development of the MetaChip technology is part of a collaborative research project seeking more efficient ways to synthesize and identify compounds that merit further development as possible new drugs.

The research is led jointly by Professor Dordick and Douglas Clark, professor of chemical engineering at UC-Berkeley, with Moo-Yeal Lee, post-doctoral research associate at Rensselaer, and Chan Beum Park, now assistant professor of chemical and materials engineering at Arizona State University, rounding out the research team. The work was supported by the National Institutes of Health (NIH).

“The availability of thousands of compounds at early stages in the drug discovery process forces chemists to select compounds for drug development based on limited information about their toxicological properties,” said Clark. “The MetaChip is the first technique to combine high-throughput metabolic enzyme catalysis with cell-based screening on a microscale platform, enabling the toxicity of compounds to be analyzed quickly and effectively.”

By combining human biocatalysts with pharmacological screening, the MetaChip rapidly identifies organ-specific drug toxicity and possible adverse drug interactions, with the potential to provide full metabolite profiling. According to the recent research findings, the approach works by successfully mimicking human metabolism at speeds consistent with high-throughput biological activity screening.

Dordick says that additional research on the technique is needed. “Our research will expand to include other cell types, compounds, and human enzymes responsible for drug metabolism, including the cytochrome P450s,” he said. “The outcome of this work may facilitate the elimination of toxic drug candidates much earlier in the drug development process, thereby allowing research efforts to concentrate on more promising and less toxic candidates.”

Biotechnology and Interdisciplinary Studies at Rensselaer
At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences to encourage discovery and innovation. Rensselaer’s four biotechnology research constellations — biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology — engage a multidisciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world’s most advanced research facilities, Rensselaer’s Center for Biotechnology and Interdisciplinary Studies provides a state-of-the-art platform for collaborative research and world-class programs and symposia.

Contact: Tiffany Lohwater
Phone: (518) 276-6542
E-mail: lohwat@rpi.edu