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Bioassays are essential tools for pre-clinical research. By revealing whether a compound or biologic has the desired effect on your biological target, bioassays can drive decision-making throughout the drug discovery process, to ultimately bring new drugs to patients.
Following our key rules of thumb below will help you start developing bioassays for reliable compound progression, to benefit all stages of your early drug discovery research.
Where do bioassays fit in early drug discovery?
As innovations in drug discovery continue to abound, there’s never been a more crucial time to ensure your research stays at the cutting-edge, so that it makes the maximum impact. This means using state-of-the-art bioassays to effectively and reliably move a candidate compound or biologic through the multiple stages of early drug discovery, leaving little doubt that your decisions are based on the highest quality data possible.
So, to leverage the full potential of your research, now’s the time to take a good look at your approach to developing bioassays. If it’s still stuck in the 20th century, it’s essential that you update your key principles to meet modern thinking. A good way to start is to take a look below at the vital role bioassays play at each stage of the early drug discovery process.
Target selection/identification: How is the target relevant to the disease, and how is your drug going to help patients?
Target validation: Check the target is relevant to disease progression and is a valid candidate for investigation
Hit discovery/hit optimisation: Develop primary, secondary and technology interference assays, and apply medicinal chemistry to optimise the compound’s potency
In vitro lead identification/lead optimisation: Perform efficacy profiling and safety testing using plate-based assays in cells relevant to the target mechanism of disease
In vivo lead discovery/lead optimisation: Use animal models of the disease to assess the target’s mechanism of action, efficacy, and safety
Candidate lead compound selection: The lead molecule will only progress to human clinical trials if it achieves the desired efficacy and safety profile
But knowing how your bioassay fits in to these various stages is only the first step towards success.
Considerations for great assay design
Your bioassay could make all the difference to finding a drug that will have a positive impact on patient’s lives. At the outset, you need to consider which bioassay is most suitable for your stage of research. Will this be:
- In isolation, using a biochemical assay
- By expression of the target in a recombinant cellular background (cell-based)
- By measuring a phenotypic response related to the bioactivity of the target
But, choosing one of these approaches isn’t as simple as it may seem. You must weigh up the pros and cons of each to work out which one best suits your research. It’s often a case of weighing up what’s more important: using a more physiologically relevant bioassay, or one that maximizes the efficiency by which you can screen thousands, and even millions, of compounds.
Driving your drug discovery forward
Applying these general principles to your bioassay development will undoubtedly help you to de-convolute compound activity to you closer to compounds that may make it into the clinic, but these insights are only the tip of the iceberg. Many more aspects of your approach may be preventing your research from reaching its full potential. For example, are you sure you are maximizing the sensitivity and specificity of your bioassays to properly prosecute your target? What are the compound’s binding properties and is it toxic to cells?
But, it’s not all doom and gloom. We know how important addressing the quality, reliability and consistency of your bioassays is to your research, so we’ve collated our best recommendations for bioassay development in our free eBook, in the hope they will help drive your drug discovery research forward!