Aberrant biochemical and metabolite signaling plays an important role in the development and progression of diseased tissue. This concept has been studied by the science community for decades. However, with relatively recent advances in analytical technology and bioinformatics as well as the development of the Human Metabolome Database (HMDB), metabolomics has become an invaluable field of research.
At the “International Conference and Exhibition on Metabolomics & Systems Biology” held recently in San Francisco, researchers and industry leaders discussed how the underlying cellular biochemical/metabolite fingerprint in response to a specific disease state, toxin exposure, or pharmaceutical compound is useful in clinical diagnosis and biomarker discovery and in understanding disease development and progression.
Developed by BASF, MetaMap® Tox is a database that helps identify in vivo systemic effects of a tested compound, including targeted organs, mechanism of action, and adverse events. Based on 28-day systemic rat toxicity studies, MetaMap Tox is composed of differential plasma metabolite profiles of rats after exposure to a large variety of chemical toxins and pharmaceutical compounds.
“Using the reference data, we have developed more than 110 patterns of metabolite changes, which are specific and predictive for certain toxicological modes of action,” said Hennicke Kamp, Ph.D., group leader, department of experimental toxicology and ecology at BASF.
With MetaMap Tox, a potential drug candidate can be compared to a similar reference compound using statistical correlation algorithms, which allow for the creation of a toxicity and mechanism of action profile.
“MetaMap Tox, in the context of early pre-clinical safety enablement in pharmaceutical development,” continued Dr. Kamp, has been independently validated “by an industry consortium (Drug Safety Executive Council) of 12 leading biopharmaceutical companies.”
By allowing for quick and accurate decisions on the safety and efficacy of compounds during early and preclinical toxicological studies, this technology may prove invaluable for high-throughput drug candidate screening, added Dr. Kamp. Furthermore, by comparing a lead compound to a variety of molecular derivatives, the rapid identification of the most optimal molecular structure with the best efficacy and safety profiles might be streamlined.