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DRUG DISCOVERY-21ST CENTURY STYLE
The way new drugs are discovered (see Chap. 2 in my book, "Drugs and the Human Body", 7th Ed.) is rapidly and dramatically changing. Until recently newly synthesized compounds would be sent to pharmacological screens to test for possible drug activity. This slow, expensive, hit-or-miss approach is rapidly giving way to an immense new undertaking involving computers, the human genone, proteomics and pharmacogenomics. The human genone project, now essentially complete, mapped the human genone, that is, determined the actual sequence of the 3.1 billion base pairs (adenine-thymine, guanine-cytosine) in human DNA. Scientists know that there are about 35,000 human genes, strung out along our 46 chromosomes, carrying instructions for making all 30,000 body proteins, including enzymes, hormones, endorphins, antibodies and tissues. The new plan for drug discovery is to identify each protein, whether beneficial to the human, or destructive (as in cancer or infectious disease). Further, the goal is to create a genetic profile for each and every one of us, and give every one a profile card to carry around in our wallet. Using the discipline of PROTEOMICS, each of us would have all our body proteins completely identified so that drugs could be synthesized to act specifically on the disease that has befallen us. In other words, the goal of proteomics (and the corollary pharmacogenomics) is to tailor drug treatments to an individual's personal genetic profile. Research in proteomics is now underway to find targets to attack ovarian and breast cancer in several women patients who have submitted blood samples for genetic profiling. This new approach for drug discovery is a far cry from the slow, hit-or-miss process used for the past 100 years.
In the discipline of PHARMACOGENOMICS, researchers study how genetic variations (we all have them) affect the way patients respond to drugs, that is, how gene differences are manifested in drug targets (receptor sites) or in any of the 400 enzymes that catalyze human drug metabolism. If you have inherited different metabolizing enzymes, you may experience different drug efficacy or even toxicity. Again, the goal is to tailor drug treatments to a patient's personal genetic profile.
The role of computer technology in this is central. Massive quantities of data on the genome and proteome must be entered, stored, and retrieved, a herculean task of information management that would be impractical without computers. This aspect of modern drug discovery, named BIOINFORMATICS, is also used to create simulated protein structures akin to those from a human gene. Bioinformatics is used today to study a gene associated with human colon cancer.
If all of this seems to you like a great, exciting, unique approach to drug discovery, it is! But it is also an immensely broad, very long-term, and difficult undertaking. Fortunately, the best research laboratories worldwide are gearing up for the assault. For more information on nomenclature, browse this glossary: www.genomicglossaries.com/content.omes.asp. A reference for proteomics is: http://www.e-proteomics.net/ . For bioinformatics, http://www.bioplanet.com/ whatis.html. |