23 June 2017 |       Share
 
 
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ALL-IN-ONE DRUG DISCOVERY

In vivo imaging mediated by genetically encoded biomarkers is poised to become one most valuable asset for improving the way new drugs are discovered and developed in the next decade.



With rep
TOP™ models it is possible to measure pharmacological parameters in the living, whole animal. Pharmacokinetics and pharmacodynamics are no more two distinct processes, but instead two faces of the same experimental plan. We are showing here how the most relevant parameters needed for target validation, lead selection and lead optimization can be resolved by our mice and how the level of information gathered through their use is much higher than with conventional approaches.


Time Course Experiments

The experiment shows that the maximal drug target activation occurs 6 hours after s.c. injection, that the drug candidate is active in the liver and that the action lasts for about 24 hours. In this experiment we apply quantitative analysis of in vivo photon emission for a first rapid evaluation of drug effects.


Dose-response studies

Dose-response studies, performed using repTOP™ mice, enable the detection of:

• the lowest active dose

• dose-dependent changes in tissue permeability

• specificity of action


Tissue distribution and drug potency

repTOP™ mice allow the comparison of drug effects in different organs and tissues. Vast arrays of compounds can be tested for rapid definition of their relative potency and tissue penetration.

Assessing lead potency towards a defined target is normally performed through cell-based assays. Studies in whole living animals may provide more complete data on drug effects in the presence of organic pathophysiological processes.




Longitudinal studies

repTOP™ mice allow the monitoring of effects of repeated administrations of a drug in the same animal over time, because in vivo imaging is non-invasive, and the same mouse can be treated and monitored for long periods.

REFERENCES

Existing repTOP™ mice can be used in several therapeutic areas. Following the examples below, you’ll find also more examples about the useful additional information they can provide when used in drug discovery and development.

·         Oncology

·         Regenerative medicine

·         Women Health

·        Metabolic diseases

·         …many others. If a model tailored to the drug target you’re investigating does not exist, yet, exploiting repTOP™ technology and its huge experience in the field, TOP srl will eagerly create the model suitable for speeding up your research.


OTHER APPLICATIONS


repTOP™ mice can be applied also to the study of

·         Toxicology

·         Nutraceuticals and functional food.