Our bioscience experts work with you to develop robust, reproducible assays that will reliably deliver throughout the drug discovery process. The team has particular expertise in developing cell-based assays.
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In early drug discovery bioassays not only reveal whether a compound acts on a biological target but also how effective it is and if it has any potentially off target effects. In turn, this can influence decisions about whether the candidate warrants further study.
The importance of bioassays in early drug discovery may be clear, yet what is less clear is how they should be developed to ensure they are optimised for their specific purpose.
Assay design and development is a complex process, involving many considerations that can each determine the specificity, sensitivity, and reliability of a compound’s action on a target. As such, if you develop your own assays, what you produce can mean the difference between valid and invalid results that help or hinder your drug discovery research.
Designing for success
Assay design is a major factor underpinning the success of any drug discovery programme. A well-designed assay should be one in which every step in the protocol has been evaluated.
One analogy is that assays are like aeroplanes; if you need to travel 500, 5,000 or 50,000 miles, you want to fly in a well-designed aeroplane and get the same outcome every flight: you arrive safely!
Whether built from literature or already existing, our focus is always on ensuring the assay is fit for purpose.
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Wide ranging experience
Our bioscience leadership has decades of large pharma experience in drug discovery gained in companies including Hoffmann La Roche, Smith Kline Beecham, GlaxoWellcome, AstraZeneca, ICI and UCB.
The wider team has worked in pre-clinical discovery, designing and developing low, medium and high throughput assays in both cellular and non-cellular assay formats.
They have experience of a wide range of technologies designed to prosecute these activities in a scalable manner whilst bringing to bear technological developments that have the ability to probe ever further into the molecular interactions from which the drugs of the future may be identified.
A culture of approaching problems as a group results in time efficient and cost effective assay development.
FAQs of assay development
We take a look at some of the most common challenges you might face when designing bioassays for early drug discovery and offer advice on how to overcome them.
How should you define a hit compound?
Usually, if the compound has an activity greater than the statistically defined noise of the bioassay, and has shown this same activity consistently when tested multiple times, then you can call it a ‘hit’. But how does this work in practice?
If you screen 1,000 compounds in your bioassay, you can rank them based on their activity. Look to determine the change observed for these compounds, when compared to your controls, and calculate this as a percentage. By plotting this as a distribution of percentage activity (on the x-axis) versus frequency (on the y-axis), you can then logically apply a ‘cut-off’ to identify the active compounds to retest.
What plate format and layout should you use for developing bioassays?
The multi-well plates used in bioassays come in different densities (i.e., 6/24/48/96/384/1536-wells), but the format you decide to use will depend on how many compounds you will be testing, and the cost of your reagents. For example, using a 384-well plate format allows you to screen more compounds at a time and decreases the well volume, so you can use your reagents more efficiently and make your experiments more cost-effective.
To find out more about optimising the plate format and layout for your bioassay development, take a look at our guidelines. These go into much more detail about how to decide on the optimal plate layout for your controls and test wells and how to miniaturise bioassays from 96- to 384-wells (it’s not as simple as reducing all the reagents by four-fold!).
What dilutions should you use for a dose-response experiment?
Performing a dose-response experiment of your standard in the bioassay, can give you greater insights into the effects of your compound. But what are the optimum dilutions to use? A good place to start is to use either one in two or half log (1 in 3.16) dilutions. Also determine the maximum compound concentration your bioassay can cope with i.e. the tolerance of the bioassay to the solvent dimethyl sulfoxide (DMSO) to prevent toxicity issues.
Here we’ve touched upon just a few of the hurdles you may encounter in bioassay development, and offered key insights into how you can overcome them to drive your drug discovery programmes forward. However, other challenges such as what to do if the Z prime of your bioassay is less than 0.5, or if you can’t access a pharmacological tool or reference compound may also arise.
In our eBook, you can read about some of the most exciting emerging bioassay technologies, such as three-dimensional cell culture and acoustic mass spectrometry, that could help you to accelerate the success of your drug discovery programme.
Blogs on assay design
The following blogs provide useful advice and guidance on assay design: