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propafenone, indecainide, ethmozine, etc.), since that is what their assays were best at picking up as active agents. Thus the model is so very important in the drug discovery process and will often determine development. We could synthesize thousands of compounds and select for development a few that fit the characteristics being sought by the model employed in the screening process, but these may not be optimum for therapy. This is a major problem and one not given enough consideration. We can only think of the possibility that there may be hundreds, if not thousands, of compounds buried in analytical hoppers such as Janssen's Bersa research establishment that could have been extremely useful, but were discarded because they were not identified as biologically active in an inherently flawed screening model. |
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In addition to the problem of the model used in drug screening there is also a fundamental difference in discovery between mass screening and receptor-targeted research. The latter has proved more successful in the last decade, but some major advances have come out of pure chemistry and follow-up screening to determine biologic activity. Can the revolution of the information age and computer sciences be applied to synthesis and screening? This is a cogent question that will challenge us in the coming years. I believe a revolution will occur here too. Synthesis on a grand scale will be tied to automated focused biological-activity screening that will permit the evaluation of tens of thousands of molecules on a daily basis. Clearly, how we screen will determine the validity of this approach. |
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While we are in transition from the age of synthetic chemistry to biotechnology and gene manipulation, synthetic discovery still will play a major role in advancing the therapeutic armormentarium. |
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IV. Biotechnology and Gene Manipulation |
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The area of biotechnology and gene manipulation is in its early stages, but has already made considerable impact. The largest pharmaceutical companies are busy positioning themselves by acquiring or joint venturing with the biotechnology companies, usually small start-up enterprises. They are undertaking these acquisitions to be prepared to benefit from the coming revolution in biotechnology and gene manipulation products and procedures. Biotechnology has not advanced as rapidly as some have predicted. The science has made tremendous strides, but a number of factors have limited the advances and commercialization. The scale-up and commercialization of biotechnology processes is limited by expense and the difficulties that are technologically imposed. The first generation of compounds have been effective at times, as growth hormone and rTPA demonstrate. However, there have been major failures such as the antibodies to counteract the effects of septic shock. While the science permits the creation of drugs to evaluate, the compounds themselves may not |
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