facebook twitter linkedin
discovery chemistry


Lead optimization

In the lead optimization stage of drug discovery process researchers must select the leads with the greatest potential to be developed into safe and effective medicines.

During this stage of drug research, one must focus not only on increasing the biological acivity, but also on a number of drug-like parameters, including: permeability, metabolic stability, lipophilicity, solubility, plasma-protein binding, CYP450 interactions, pKa, PK/PD, etc. Preclinical lead optimization technologies must be sufficiently rapid to interface with high-throughput screens without creating a further pipeline bottleneck, be predictive of drug failure, and be highly cost-effective.

Our company provides the comprehensive set of computational methodologies to help drive your lead optimization programs. Selvita helps its customers in the improvement of compound pharmacological profile (affinity, selectivity). Our expertise in pharmacophore modeling and rational ligand design techniques will increase the chances of obtaining valuable preclinical drug candidates.

We also have experience in the utilization of more sophisticated and computationally expensive apporaches of theoretical chemistry, like FEP (free energy perturbations) or quantum mechanical methods. Those can be used to very in a very efficient way the desired modifications in the lead structure if high quality structural information is available (eg. X-ray structure).

Another group of lead optimization methods extensively developed in Selvita is ADME/Tox properties prediction with the use of QSAR technologies, both literature-based and custom. We perform the complex, multi-parameters analyses of compound metabolism. For the compound and its metabolites we are able to asses not only possible side effects, like hERG channel activity or inhibition of CYP450 isoforms, but also estimate the compound broad biological profile based on possible interactions with known biochemical pathways, which is a starting point to compound profiling.