ServicesLead selection

Which is the best lead compound to take into pre-clinical studies?

Physiomics can help its partners take the best decision.

A top 10 pharma asked us to determine the optimal inhibition ratio for two targets in order to select the lead compound in a dual kinase inhibitor family. A model was built to assess the level of synergy between the two targets and select the compound having the optimal balance. The model was calibrated using our partner's data and was used to evaluate the effect of inhibiting both targets (Figure 1). Our simulation correctly predicted experimentally observed outcomes, confirming the robustness of our model.

Lead selection – figure anonymised

Fig. 1 Using the model it is possible to decouple the mechanisms of action A and B and evaluate the overall dose-response effect on the cell cycle according to the level of inhibition of each target. The white line through the graph corresponds to the dose-response profile of one compound in the family.

The knowledge gathered from the simulation results could be used to rank the compounds and select the best one in the family.