InteliSpark client, Zymtonix Catalytic Systems, has been awarded a Phase I SBIR grant from the National Institute of Environmental Health Sciences (NIEHS) for their project “A High-Throughput Cell-Free Profiling Platform Integrating High Metabolic Diversity for Chemical Safety Assessment”.
Each year, there are roughly 2,000 new drugs and chemicals that meet the safety requirements of regulators (e.g. the U.S. Food and Drug Administration), and are commercialized. Early screening for unsafe compounds to “fail fast” are essential to research and development programs, prior to animal or human testing. In vitro toxicity assays are the primary method of screening, yet they are unable to assess the contribution of potentially toxic metabolites that the body produces from otherwise safe parent chemicals. Therefore, the integration of metabolic profiling into toxicity screening is crucial to chemical risk, exposure and drug safety assessments.
The cytochrome P450 (CYP) family is one of the most important families of enzymes for human metabolism. About 75% of all xenobiotics and drugs are metabolized in the liver. Using the function of CYPs and other metabolic families in drug metabolism and pharmacokinetics are crucial to increasing the safety of drugs and increasing their development. Current methods mimic liver physiology, yet there are drawbacks such as limited incubation time and metabolite production, the need to statistically evaluate significant background metabolomes, and complex quality control challenges in cell handling techniques.
With their grant funding, Zymtronix will be able to develop a novel, cell-free technology that offers increased metabolite production, enzyme specific metabolomes with little background, and improved quality control, allowing for reduced cost and ease-of-use. They will then move onto Phase II research to explore a larger number of chemical substrates with an expanded set of CYPs/UGTs to determine a critical set of metabolic enzymes that produce a diverse and physiologically relevant metabolome.