- •Drug design
- •Approaches
- •Types
- •Ligand-based drug design
- •Structure-based drug design
- •Scoring method
- •Computer-aided drug design
- •Computational Techniques in the Drug Design Process
- •Techniques develop
- •Financial Aid
- •Main Compounds
- •ISOLATION
- •Refine
- •Testing
- •Formulation
- •Production
- •Marketing
- •NON-PERSCRIPTION SALES
- •Where is a list?
- •http:// www.ccl.net/cca/documents/dyoung/topics-o rig/drug.html
Techniques develop
DEVELOP AN ASSAY
Develop an assay technique to test drug effectiveness. An ideal assay is one in which a compound can be added to tissue samples or micro-organism colonies and there will be a visible indication of an effective treatment.
At worst, there must be a way to test the drug on a laboratory animal that is susceptible to the disease. If the only way to test the effectiveness of a trial compound is to inject an untested compound into a human subject then there
Financial Aid
CONSIDER FINANCIAL ISSUES
The next step is to make a financial decision about whether to proceed with the development process.
The assay technique will determine the cost of testing compounds. If there are existing chemical treatments, it will be a refinement effort which saves the expense of finding lead compounds.
All drugs must go through extensive testing so this is a fairly fixed cost. There may be governmental grants or tax incentives associated with certain diseases.
The number of patients requiring treatment and merits of existing treatments will determine the long term profitability of producing a drug.
Main Compounds
FIND LEAD COMPOUNDS
Lead compounds are compounds that have some activity against a disease. These may be only marginally useful and may have severe side effects. However, the lead compounds provide a starting point for refinement of the chemical structures. Lead compounds may come from many sources, including
The isolation of active compounds from traditional remedies.
The testing of natural materials followed by an isolation effort.
Drugs effective against similar diseases.
Use of combinatorial chemistry techniques which produce large numbers of related chemical compounds.
Searching chemical databases to find compounds similar to those found by the above means.
ISOLATION
ISOLATE THE MOLECULAR BASIS FOR THE DISEASE
If it is known that a drug must bind to a particular spot on a particular protein or nucleotide then a drug can be tailor made to bind at that site. This is often modeled computationally using any of several different techniques.
Ideally a x-ray chrystallography structure is desired, but biomolecules are very difficult to chrystalize.
Another very useful technique, called "distance geometry" is to find some of the internuclear distances using NMR Nuclear Overhauser Effect experiments then find molecular geometries that have these distances
The difficulty in find geometries makes it possible to bring first generation drugs to market by refinement of lead compounds without ever knowing the target site for the drug in the body.
Refine
REFINE DRUG ACTIVITY
Once a number of lead compounds have been found, computational and laboratory techniques have been very successful in refining the molecular structures to give a greater drug activity and fewer side effects.
Computationally, the technique used is known as QSAR (Quantitative Structure Activity Relationships). It consists of computing every possible number that can describe a molecule then doing an enormous curve fit to find out which aspects of the molecule correlate well with the drug activity or side effect severity.
Another important aspect of the molecular structure is its solubility. Whether the molecule is water soluble or readily soluble in fatty tissue will affect what part of the body it becomes concentrated in.
Testing
DRUG TESTING
Once a drug has been shown to be effective by an initial assay technique, much more testing must be done before it can be given to human patients. Animal testing is the primary type of testing at this stage.
Formulation
FORMULATION
Before a drug can be produced, there must be a means to administer it. Ideally, a tasteless or bland tablet can be created.
Alternatively, an oral liquid, intravenous injection or directly applied cream may be created.
Production
PRODUCTION
The large scale production of complex molecules can be very difficult. Compounds originally isolated from natural products may continue to be harvested.
Drugs have a high value per gram. As such production techniques can be viable even though they are far more inefficient than those used by bulk chemical producers.
It is now also important to determine what by-products will result from production and what environmental impact there will be.
Marketing
MARKETING
If there is only one available treatment for a disease, it is only necessary to see that physicians know about it.
If there are several competing treatments, there may be quite a bit of marketing done so that physicians will understand the relative merits of each.
NON-PERSCRIPTION SALES
After a large amount of experience under a physicians supervision, a drug may be approved for over-the-counter sales. This is often the biggest profit making end of the pharmaceutical industry.
GENERIC PRODUCTION
Once the chemical patents have expired, a drug can be produced by any manufacturer. Generic drugs are often less expensive for the consumer and yield a low profit margin for the producer. The production of generic drugs favors the most cost effective production process.
http://www.youtube.com/watch?v=3Gl0gAcW8rw&fea ture=related