While drug discovery objectives don’t change, the methods and techniques by which pharmaceutical companies discover new drugs are evolving at a significant pace – and they need to.
Fremont, CA: The average cost incurred by a major pharmaceutical company for developing a new drug is over USD 6 billion. It is evident that the pharmaceutical industry is gripped by rising failure rates and costs and suggests that the cost of new drugs will be reduced by new technologies and a deeper understanding of biology. Drug discovery scientists are focused on identifying compounds and candidate drugs with ‘good’ properties that are safe and productive, as fast and cost-efficiently as possible. The standard approach has been to identify a single molecule disease target and then determine a compound that interacts with and modulates this target with high specificity. However, it is now seen that this ‘one target – one drug’ approach does not work well. That vast screening library of compounds against one particular property of an isolated target is inefficient to discover potential drugs. Most of the innovation currently seen in drug discovery methodologies seek to access and integrate more information – about targets, compounds, and disease phenotypes – to enable a more comprehensive and holistic approach to discover ‘good’ drug candidates.
Mass spectrometry (MS) has been continuously used to assay the metabolism of compounds in lead optimization and preclinical development for 20 or more years; fewer drugs now fail as a result of pharmacokinetic issues thanks to MS. The increasing size of chemical libraries, high throughput screening (HTS) technologies that enable thousands or millions of compounds to be screened, and the concomitant increase in compounds requiring optimization over this period have increased the urgency for the bioanalysis of metabolites, and a need for faster turnaround. In addition to new analytical techniques for MS that give more sensitivity and require less sample preparation, there has also been a drive to increase the throughput of MS.
The importance of MS is already established, but there are a growing number of label-free technologies that are either already improving, or have the potential to enhance, drug discovery. A recent conference dedicated to label-free technologies highlighted some technologies poised to become established drug discovery tools.