Screening
“We use HCS more in the hit validation stage when we want to look at what the compound is doing in more detail. It comprises about 10% of our screen- ing at the moment with secondary and ADME-Tox screening the bulk of the effort. We have all the technology we need and I anticipate we will use HCS more as phenotypic screening increases.” Pharma/Biotech HTS Lab
Figure 1: Proportion of HTS laboratories using HCS technologies © HighTech Business Decisions
“We use HCS in a number of different ways. We have to be careful because it is such a commitment to assay development and image analysis. We don’t want to use HCS if we can use something else instead. We use it for follow up of morphology types of assays. They are sensitive for measuring activity in primary and iPS cells. Imaging is a good readout for neuronal cells and T-cells. We use HCS for lead optimisation, follow-up and primary screens of targeted libraries, for example, repur- posing FDA-approved drugs. It is not so good for looking for new chemistry. But, is it worth it? The trend in pharma is HCS seems to be going down a little. It needs to be used for the right indication. In the future, what needs to happen is the equipment needs to get cheaper so that it can inundate gov- ernment and university biology labs so more and better assays can be developed. Then we will final- ly see more penetration of HCS in drug discovery. We need the biologists to explore this type of capa- bility in disease-relevant cells with better software and processing power.”
Academic AS
Figure 2: HCS adoption by segment © HighTech Business Decisions
For those HTS laboratories using HCS, there has been an increase use of HCS in both primary and secondary screening over the past five years (Figure 5). The proportion of HTS laboratories using HCS technologies for both their secondary and primary screens has increased considerably over the past five years. In 2012, 84% of the HTS laboratories used HCS for secondary screening, compared to 53% in 2007. Similarly, 48% of the HTS labora- tories used HCS for primary screening activities in 2012, compared to 27% in 2007.
Below are selected comments from directors at leading HTS laboratories regarding the use of HCS in their operations.
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“We have used HCS for primary screens as well as secondary assays and for cytotoxicity studies to characterise our library. In the next five to 10 years, we will increase the number of phenotypic assays we do. We are interested in collecting data on a per cell basis and measuring multiple parameters.” Academic HTS Lab
“We only use HCS for secondary assays. Sometimes HCS is the only real readout we can use, we did not have any other method to assay the target. We also use it for different projects outside screening, for example, we will use the microscope to see if we are staining the cells properly.” Pharma/Biotech HTS Lab
While there is an increase use of HCS, several HTS laboratory directors see barriers to its contin- ued adoption. Most of the barriers associated with the adoption of HCS relate to the costs and bene- fits of HCS compared to traditional screening tech- nologies. As noted by one HTS Director: “We use
Drug Discovery World Spring 2013
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