Dear Colleagues,

Productivity of the pharmaceutical industry measured in terms of a number of approved drugs has been in decline over the last several decades. New creative approaches in drug design have been put in place to reverse that trend. Structure-based drug design that relies on high resolution 3D structures of drug targets is being complimented with fragment-based drug design approach which utilizes NMR spectroscopy to shorten the time of lead generation. On the other hand, closer attention is drawn to a drug-likeness of molecules – molecular weight, solubility, lipophilicity, etc. Lipinski's rule of five or its modifications are gaining prominence in medicinal chemistry decision making. Cheminformatic tools are becoming part of arsenal for medicinal chemists. Drug design takes into account not only pharmacological properties, but also potential toxicological effects of the molecules. Potential for reactive metabolite formation and protein covalent binding now can be assessed with various successes in vitro to predict idiosyncratic toxicity in clinic. New procedures including in silico models can be implemented to predict pharmacokinetic properties of the compounds.
Prevailing dogma in drug discovery that values selective compounds the most is getting challenged with a concept of polypharmacology, which suggests that multitargeted drugs, compared with selective drugs, may display better efficacy in clinic. As far as the mechanism of drug action goes, concept of allosteric modulation is more widely employed in a number of therapeutic areas.

Dr. Arthur Gomtsyan
Guest Editor

• structure-based drug design
• fragment-based drug design
• drug-likeness, rule of five
• cheminformatics
• predictive methodologies for ADME and drug toxicity
• polypharmacology
• allosteric modulators