Molecular Design in Drug Discovery: Applications and Challenges
Karl-Heinz Baringhaus, Gerhard Hessler, Hans Matter and Christian Buning,
Molecular Design plays an important role in modern Drug Discovery. It is applied in lead generation for turning hits into leads and in lead optimization for fine-tuning of leads.
This presentation outlines Molecular Design principles in particular in small molecule lead optimization. For example, application of our SALI Explorer in structure-activity relationships (SAR) fosters the early identification of SAR hot spots within lead series. Subsequent quantitative structure-activity relationship is then applied to optimize compounds against the target of interest.
Most often lead series suffer from not acceptable ADMET profiles and/or anti-target activities. We have implemented several predictive data mining tools in the field of ADMET- and anti-target (e.g. hERG, CYPs) modeling. A few examples outline the scope and applicability of these tools for Medicinal Chemists and Drug Designers. In addition, in silico profiling of molecules against off-targets allows fast and early identification of liabilities of putative lead series.
The increasing interest in peptides and biologicals (e.g. proteins, antibodies) as drugs opens new opportunities for Molecular Modeling. For example, peptide design becomes more and more important in order to synthesize only the most active peptides while taking into account their physicochemical properties.