Effective Use of In-Silico Tools in Lead Optimization

A key element for successful utilization of in silico tools in lead optimization is mechanistic interpretability of predictive models. Rational strategy of lead optimization should aim at achieving balanced physicochemical profiles of candidate compounds that would translate into the desired ADME properties. In those cases when a successful compound does not follow general rules, local models (pairwise QSAR) might help in achieving the desired balance.