Rational Drug Discovery
In contrast to traditional methods of drug discovery, which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design begins with a hypothesis that modulation of a specific biological target may have therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces of information are required. The first is evidence that modulation of the target will have therapeutic value. This knowledge may come from, for example, disease linkage studies that show an association between mutations in the biological target and certain disease states. The second is that the target is "drugable". This means that it is capable of binding to a small molecule and that its activity can be modulated by the small molecule.
Once a suitable target has been identified, the target is normally cloned and expressed. The expressed target is then used to establish a screening assay. In addition, the three-dimensional structure of the target may be determined.
The search for small molecules that bind to the target is begun by screening libraries of potential drug compounds. This may be done by using the screening assay (a "wet screen"). In addition, if the structure of the target is available, a virtual screen may be performed of candidate drugs. Ideally the candidate drug compounds should be "drug-like", that is they should possess properties that are predicted to lead to oral bioavailability, adequate chemical and metabolic stability, and minimal toxic effects. Several methods are available to estimate druglikeness such as Lipinski's Rule of Five and a range of scoring methods such as Lipophilic efficiency. Several methods for predicting drug metabolism have been proposed in the scientific literature, and a recent example is SPORCalc. 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.
Read more about this topic: Drug Design
Famous quotes containing the words rational, drug and/or discovery:
“There has never been in history another such culture as the Western civilization M a culture which has practiced the belief that the physical and social environment of man is subject to rational manipulation and that history is subject to the will and action of man; whereas central to the traditional cultures of the rivals of Western civilization, those of Africa and Asia, is a belief that it is environment that dominates man.”
—Ishmael Reed (b. 1938)
“Behind the steering wheel
The boy took out his own forehead.
His girlfriend’s head was a green bag
Of narcissus stems. “OK you win
But meet me anyway at Cohen’s Drug Store
In 22 minutes.””
—John Ashbery (b. 1927)
“We early arrive at the great discovery that there is one mind common to all individual men: that what is individual is less than what is universal ... that error, vice and disease have their seat in the superficial or individual nature.”
—Ralph Waldo Emerson (1803–1882)