BioFocus homepage

search

Mailing list

Compound screening in disease-relevant complex assays

 

As our understanding of the complex interplay of networks and pathways within cellular processes increases, the need for ways to screen compounds in the correct disease context also grows.  Disease-relevant assays in human primary cells that are amenable to high-throughput screening allow you to accelerate drug discovery by finding the right lead candidate quickly.

 

 


BioFocus DPI has extensive experience screening in disease-relevant human primary cells with functional readouts in medium and high-throughput. We offer customized assay development and screening using our adenoviral toolkit with readouts including high-content screening and multi-parameter detection (Meso Scale Discovery). With quality systems applied throughout the process - from cell culture to data analysis - we deliver data you can trust*.


Track record

We have developed 17 medium- and high-throughput customized human primary cell assays for screening in 14 different disease areas with an average of 15,000 data points per screen.

 

The below list illustrates the types of cells we have successfully screened. We can also work with you to develop new assays relevant to your specific disease area.

 

• Endothelial cells

• Smooth muscle cells

• Skeletal muscle cells

• Synoviocytes

•Chondrocytes (3D and monolayer)

• Fibroblasts

• Dendritic cells

• Mast cells

• (Pre-)adipocytes

• Mesenchymal stem cells

• Osteoblasts

• Monocytes

• Hepatocytes

• Macrophages

• Keratinocytes

• Differentiated neuronal cells

• Embryonic stem cells

• Human cell lines (3D and monolayer)

          



Case studies 

1. In an assay developed in collaboration with Cystic Fibrosis Foundation Therapeutics, we measured functional restoration of chloride channel activity of CFTR-delF508 in patient derived cells using the small molecule “compound corrector 4a”, known to restore CFTR activity (Figure 1A). We then performed a pilot screen using the same assay on the BioFocus DPI natural product library (Figure 1B).

 


2. In rheumatoid arthritis, synovial fibroblasts release a range of inflammatory mediators that maintain the inflammation in the joint. Mediator release can also be used as a PrimePath assay.

 

Figure 2A shows release of an inflammatory mediator by synovial fibroblasts from rheumatoid arthritis patients after stimulation with a cytokine. Figure 2B shows inhibition of mediator release by dexamethasone. Figure 2C shows an

example of screening test compounds using this assay. In this figure, the blue circles are measurements of background release; orange circles are release after stimulation; green circles show inhibition of stimulated release by dexamethasone and gray circles show the effects of test compounds.

 


Contact us to learn more about using PrimePath in hit finding, hit-to-lead and lead optimization.


 

*Biofocus DPI’s quality management system is ISO-9001:2000 certified

 BioFocusฎ, PrimePath™ and SoftFocusฎ are trademarks of Galapagos NV and/or its affiliates



Galapagos   Copyright © 2008 BioFocus DPI plc Log in |  MoveNext - Latus