A tissue-specific molecular pharmacology protocol example

We are pleased to present an example of the tissue-specific molecular pharmacology protocol for drug development.

In collaboration with our partners we can enhance the readout of in vivo / ex vivo pharmacology study by evaluating the drug candidate mode of action at a cellular level, by providing molecular pharmacology data in various tissue compartments and by identification/validation of molecular targets.

Cell behaviour in health and disease is intricately linked to the microenvironment of cells. Studying in vivo cell dysfunction and responses to drugs is what matters, but the interpretation of whole tissue analysis is often hampered by the complexity of the tissue.

Our approach assigns drug effects and cell behaviour in complex tissue to certain cell types. This compartmentalization will provide a better insight in the true pharmacological behaviour of your new compound in relation to the disease status.

To download the protocol example, please click here.

Experiment summary example

Study setup

A gene essential for the efficacy of your drug candidate has been identified. The efficacy study can be designed to monitor the expression levels in predestined cells or tissue compartments, both during and at the study end-point.

Samples

The analysis can be performed on various samples, e.g. tumor sections, whole tumors &biopsies.

Results

The table below shows the expression levels in different compartments of the tumor and surrounding healthy tissue, and endothelial tumor cell line.

Conclusion

1. Laser microdissection was successful, resulted in successful enrichment of analysed genes.

2. The gene D and E are highly enriched in the tumor blood vessel compartment, comparable to the gene B which is considered to be a pan-endothelial marker gene.

3. The gene F and gene G are not enriched in the tumor blood vessel compartment.

Additional information about tissue-specific molecular pharmacology drug development can be found in the following scientific papers:

• Innovations in studying in vivo cell behavior and pharmacology in complex tissues – microvascular endothelial cells in the spotlight.
• Vascular endothelial growth factor receptor 2 inhibition in-vivo affects tumor vasculature in a tumor type-dependent way and downregulates vascular endothelial growth factor receptor 2 protein without a prominent role for miR-296.