Increase the chances of clinical efficacy
Benefits
The efficacy of inhibiting a target is commonly dependent on the residence time of the inhibitor. This implies that two different ligands with identical affinity could differ significantly in clinical efficacy due to differences in kinetics. Therefore, understanding the structure-kinetics relationships will give you an advantage in the development of a new drug.
Deliverables
1) A quantitative model for kinetics
2) A structural interpretation of the structure-kinetics relationships
3) Identification of kinetic hot spots
4) Conceptual platform for structure-kinetics optimizations
Technical Details
The strategy developed by Beactica for calculating quantitative structure-activity relationships and to make a structural interpretation of the result is based on a combination of several techniques, as illustrated in the figure. In the first part of the scheme, selected ligand-based descriptors important for describing the kinetics are calculated. By combining the ligand-based descriptors with interaction-based descriptors, multivariate modelling could provide a quantitative model for the kinetics. This model also provides the basis for a structural interpretation and the identification of kinetic hot spots within the protein. A pharmacophore approach works as an alternative, fully ligand-based method.
Figure. Workflow used at Beactica to model quantitative structure-kinetics relationships.
