How New Drugs are Developed: Improve the Lead Compound
Pp. 163-176 (14)
Robert E. Smith
To improve the lead compound, chemists can design rational drug. They can
systematically alter the structure of the lead compound to yield different compounds
that are more effective and present fewer side effects. The structures of compounds
drawn in silico can be docked to the target proteins and interaction energies calculated.
Databases of biochemical and medicinal interactions can be evaluated using network
theory to find new targets for therapy. Computer programs can be used to calculate
molecular and quantum mechanical descriptors, which can be correlated to the
measured properties in a quantitative structure-activity relationship, or QSAR. Other
tools of rational drug design are to model molecular structures and their binding to
potential targets, to perform combinatorial synthesis and high throughput screening for
any of a number of biological effects. One can also look for the genetic cause of a
disease and a way to deliver the correct gene into the patient in gene therapy.
Rational drug design, QSAR, combinatorial synthesis, high
throughput screening, Once the pharmacokinetics and toxicokinetics of a lead
compound has been identified, the next step is to try to find an improved lead
compound that is more effective, has fewer side effects and has lower toxicity.
Adjunct Assistant Professor Park University and Consultant Science Advisor United States Food and Drug Administration (FDA) USA