Rational drug design | method of drug design

Rational drug designing

Unlike the historical method of drug discovery, by trial-and-error testing of chemical substances on animals, and matching the apparent effects to treatments, rational drug design begins with a knowledge of specific chemical responses in the body or target organism, and tailoring combinations of these to fit a treatment profile.
Due to the complexity of the drug design process two terms of interest are still serendipity and bounded rationality.
Those challenges are caused by the large chemical space describing potential new drugs without side-effects.
A particular example of rational drug design involves the use of three-dimensional information about biomolecules obtained from such techniques as x-ray crystallography and NMR spectroscopy.
This approach to drug discovery is sometimes referred to as structure-based drug design. The first unequivocal example of the application of structure-based drug design leading to an approved drug is the carbonic anhydrase inhibitor dorzolamide which was approved in 1995.
Another important case study in rational drug design is imatinib, a tyrosine kinase inhibitor designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosome-positive leukemias (chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous drugs for cancer, as most agents of chemotherapy simply target rapidly dividing cells, not differentiating between cancer cells and other tissues.

The activity of a drug at its binding site is one part of the design. Another to take into account is the molecule's druglikeness, which summarizes the necessary physical properties for effective absorption. One way of estimating druglikeness is Lipinski's Rule of Five.