Safety assessment

For many pharmaceutical companies, drug safety assessments are still made fairly late in the drug discovery process. However, it is clear that safety testing should be one of the first steps in the selection of lead compounds, especially when a great variety of compounds exist to support the creation of structure-activity relationships. The adoption of newer in vivo, in vitro and in silico tools and the use of new and promising technologies must be the priority for pharmaceutical companies in order to increase drug safety.

It is now apparent that mitochondrial toxicology has become an area of interest to the industry, since a primary assessment of mitochondrial toxicity of a range of compounds can be performed in a fast and relatively inexpensive way, avoiding some later human toxicity problems that may arise during subsequent testing stages or even during clinical use. Indeed mitochondrial dysfunction is increasingly implicated in the etiology of drug-induced toxicities. Members of diverse drug classes undermine mitochondrial function, and among the most potent are drugs that have been withdrawn from the market, or have received Black Box warnings from the FDA. To avoid mitochondrial liabilities, routine screens need to be positioned within the drug-development process. We should expect to see in the future an increasing number of pharmaceutical companies establishing protocols to assess mitochondrial toxicity of novel molecules under study in a fast and inexpensive way.

Since the dominant function of mitochondria is the production of cellular energy through OXPHOS, the assessment of mitochondria health and impairment has become the focal point of mitochondrial analysis. However, most traditional techniques for such analyses suffer from low throughput, time-consuming mitochondrial isolation steps and the non-physiological conditions associated with the detachment of mitochondria from the cellular environment. INTEGRACELL quantitatively detect multiple intact mitochondria OXPHOS complexes from cell lysates or tissue extracts. These panels demonstrate the potential broad applications in the study of mitochondria dysfunction-associated diseases in order to better understand disease mechanisms and to discover potential treatments. They can potentially be used in the drug development process to predict mitochondrial impairment-linked drug-induced toxicity, thus correspondingly reducing late-stage drug attrition and improving drug safety.