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High-Content Biology and Screening is a powerful approach to drug discovery

High Content Biology and Screening IRBM

The process of drug discovery and development involves different in vitro experimental models (high-content biology and screening) to:

  • Evaluate drug efficacy in the relevant cell model
  • Eliminate toxic compounds and evaluate drug-drug interaction potential
  • Select compounds for animal studies
  • Predict human in vivo properties

High-Content Biology and Screening IRBM

We apply high-content technology throughout the drug development pipeline. Our offerings include primary compound screening, qualitative secondary assays for supporting SAR, early evaluation of ADME/toxicity properties, and multi-dimensional drug profiling. Selection of the appropriate in vitro tools depends on scientific hypotheses that arise during the previous stages of drug discovery. Our experimental strategy involves different model systems, requiring stepwise or parallel integration of the information generated.

We can run multiplexed analysis in 2D and 3D cell cultures and extract quantitative data from cell populations. To do so, we use laser-based wide-field and confocal imaging, as well as medium-high throughput screening (including fluorescence-based, luminescence-based, and mass-spectrometry-based assays). We are also able to monitor and quantify complex drug-induced phenotypic changes in sophisticated disease models. These include primary cells, tumor cell lines, stem cells or iPSC-derived cells, as well as 3D spheroids.

In our organ-specific toxicity assays, we can simultaneously monitor different phenotypic parameters associated with toxicity in a single, complex biological system. These include general parameters such as viability, apoptosis, oxidative stress, mitochondrial dysfunction, or more specific parameters like phospholipidosis and neurotoxicity. These multi-endpoint analyses combine the general assessment of toxicity with mechanistic information underlying the observed toxicity.

2D and 3D cultures of primary hepatocytes constitute one of the models used for the evaluation of the drug-drug interaction potential of drug candidates.

To model human brain diseases, stem cells are used to address neurodegenerative disease mechanistic questions and support drug screening campaigns. Using human-induced pluripotent stem cells as a new source for modeling the blood-brain barrier (BBB), we can model BBBs with specific genetic backgrounds and in the context of disease susceptibility. This is an invaluable tool for understanding BBB dysfunction and molecular mechanisms involved in mediating CNS pathologies. It may also provide insights for targeted prophylaxis and therapies aimed at the BBB.

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