Drug compound discovery

It is important to keep in mind that safety assessment is only one of many components involved in the discovery and development of new pharmaceuticals. The entire process has become enormously expensive, and completing the transit of a new drug from discovery to market has to be as efficient and expeditious a process as possible. Even the narrow part of this process (safety assessment) is dependent on many separate efforts. Compounds must be made, analytical and bioanalytical methods developed, and dosage formulations developed, to name a few. One needs only to refer to Beyer (1978), Hamner (1982), Matoren (1984), Sneader (1986) (a good short overview), Zbinden, (1992) or Spilker (1994) for more details on this entire process and all of its components. 

The time required for the development of a drug from discovery to production can take at least 7 15 years. In many countries, patents normally run for 20 years from the date of application. Consequently, the time available for a manufacturer to recoup the cost of development and show a profit is rather limited, which accounts for the high cost of some new drugs. Furthermore, it also means that some compounds are never developed because the patent protected production time available to recoup the cost of development is too short. 

With a compound discovery method in place that achieves high potency and specificity, all that remains for aptamers to have utility as drugs would be stability, pharmacokinetics, toxicity, and low immunogenicity of aptamers in vivo. Because the literature was clear about the major human plasma endonucleases that destroy RNA molecules, one early event in the NeXstar... 

Whether strong control of FWER or FDR is appropriate in the analysis of microarrays may depend on how the inference on differential gene expressions is used subsequently. In one form of drug discovery, genes are first screened for differential expressions under normal and disease conditions. Subsequently, nucleotide sequences in the promoter regions of the genes selected in the first step are mined for unusually common sequences (called consensus motifs). Proteins (transcription factors) that bind to these motifs then become candidates for drug compounds to intervene with the disease process. 

Fig. 1 The dual role of RNAi technology in drug development process. RNAi compounds are being extensively used as a drug target discovery and validation tool. At the same time, they hold the promise of being used as drugs themselves. HTS, high-throughput screening of small molecules ADMET, absorption, distribution, metabolism, excretion, toxicity studies.

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