Phenotypic Screening Assays

You are here:

Phenotypic screening assays provide a strategic approach to drug discovery to identify lead compounds based upon their ability to induce an effect or phenotypic change in a disease relevant cell scenario.

At Charnwood Discovery, our experienced bioscientists can advise and guide you through this process to achieve candidate drug selection.

Approach to Phenotypic Screening Assays

Traditionally, two main approaches have dominated the drug discovery process. Where a drug target has been identified, target-based screening provides a quick and efficient way to identify candidate molecules. 

However, drug selection is often based upon the activity seen against a single target or mechanism. Therefore, there is a risk that efficacy and potency will not translate well to the clinical situation.

In contrast, phenotypic screening does not require prior knowledge or identification of a drug target. Instead, compounds are tested upon cell-models which represent a disease-like scenario effectively recreating the disease in a microplate format. Phenotypic screening therefore identifies compounds that can cause an observable physical change within a biological system that mimics the disease of interest. 

Phenotypic changes can be monitored beyond a single cellular response and assays can often be multiplexed to give a more informative profile of the compounds tested. As compounds are screened in a more biologically relevant scenario this helps to mitigate the risk of downstream failure as candidate compounds transition from the preclinical to the clinical phase of drug discovery.

What does a Phenotypic Screening Cascade Look Like?

Phenotypic screening does not rely upon the prior identification of a target. Target identification and validation occur much further along the screening cascade than traditionally seen with target-based screening.

Phenotypic screening assays cascade image

Robust Biological Model Development

Our scientists can guide and inform you on the development of the most robust biological relevant model for your intended disease area. We can advise upon the growth of cells whether that be:

  • Primary
  • iPSC-derived,
  • Mono- or co-cultures

We also have expertise working within a 2- and 3D format to provide detailed phenotypic measurements.

Charnwood Discovery offers a suite of technologies to facilitate the design and implementation of phenotypic screens. 

Assay platforms based upon live-cell imaging and high content imaging allow rapid identification of hits which can be analyzed based upon multiple factors. Our Attune NxT plate-based flow cytometer offers a high throughput method to apply complex and multi-parameter analysis to cell suspensions.

Phentotypic screening assays Attune

At Charnwood Discovery our scientists have expertise in two main aspects which help facilitate the development of robust and informative phenotypic assays.

Our bioscientists are skilled at working with a wide range of cell lines from immortalized cell lines to iPSC cell-based models to patient derived stem cells. This ensures the generation of information-dense data within an appropriate and disease-applicable cellular background. In addition, we can work within a 2D, and 3D format, the latter of which allows for a more biological relevant scenario.

The team can apply their knowledge and experience to develop phenotypic assays using our multiple screening platforms. We tailor and develop assays according to your needs to achieve your goal. The power of cell imaging is harnessed in both a live and fixed cell-mode to monitor cell function. 

These systems enable high-throughput image acquisition and the complex analysis required for multiparametric phenotypic assays. Our plate-based flow cytometer also enables the acquisition of multiparametric phenotypic based assays. This is complemented by the ability to analyze and monitor numerous phenotypic changes.

FAQs of Phenotypic Screening Assays

Phenotypic screening assays are conducted in a cellular model which represents a biological process or disease state. Compounds are identified by their ability to induce phenotypic changes such as a modification in the size and shape of a cell. 

Phenotypic screening initially works to identify those compounds that induce a positive phenotypic change in the system in which it is being tested. Classification of the drug target and its mechanism of action are established secondary to the initial identification of lead molecules.

Phenotypic screening is a powerful approach to drug discovery especially when the target is unknown, or the disease mechanism is undefined. Phenotypic screening provides a large quantity of information within a disease relevant scenario. 

In addition to identifying compounds with a positive effect on phenotype, this method of screening also identifies compounds with undesirable features. These include toxicity, poor cellular permeability, and decreased compound stability. 

Therefore, this leads to a much richer source of drug candidates compared to those obtained within a target-based screen.  

Examples of Phenotypic Screening at Charnwood Discovery

Designing Assays for Success

Assay design is a major factor underpinning the success of any drug discovery program. 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 i.e. that you arrive safely!

Whether built from literature or already existing, our focus is always on ensuring the assay is fit for purpose.

Download our eBook to find out more.

Assay Development