- We use phenotypic profiling of human 3D tissues to evaluate compound activity against specific targets. These assays also detect off-target effects allowing compound ranking based on activity and selectivity, enabling selection of the best compounds for further development.
- – Models available for receptor and non-receptor kinases, including EGFR, HER2, HER3, c-Met.
- – Assays for bi-specific molecules and antibody-drug conjugates.
Example: c-Met assay
Activation of the target, in this case c-Met with HGF, induces a characteristic change in phenotype. Inhibition of c-Met with a selective inhibitor induces a reversal of the phenotype. A compound that has off-target effects will induce additional phenotypic changes not associated with c-Met inhibition. OcellO’s analysis methods extract very detailed quantitative measurements to build up a profile of the response to a compound, allowing compound classification. To develop an assay for a specific target, several cell lines (selected from the ATTC collection or other source) are tested for their response to the ligand, the inhibitor or a combination of both. Cell lines are selected that show a strong target-specific change in phenotype.
The change in phenotype is expressed by a change in position in the PCA plot (upper left and right). This change can be dose-dependent, as is shown in the graphs below.
The selected assay is used to screen test compounds. Tissue phenotypes are profiled and compounds are ranked according to similarity to a reference inhibitor.
Using this approach the most selective inhibitors for a specific target can be identified, such as compound B (right panel) in this example. This technology also discriminates inhibitors that have off-target effects, such as compound B (left panel), which was withdrawn from phase III clinical trials, but received a poor ranking in our assay and would not have been selected for further development. Our technology therefore allows the best (active and selective) compounds to be identified.
For more information on our range of target based assays or for custom development of assays for your target, please contact us: [email protected]