ReviewTarget-based drug discovery: is something wrong?
Section snippets
Target-based drug discovery
A target is usually a single gene, gene product or molecular mechanism that has been identified on the basis of genetic analysis or biological observations [9, 10, 11, 12, 13, 14]. The literature does not distinguish between target classes, but for the present analysis they will be divided into two classes: genetic or mechanistic targets. Genetic targets represent genes or gene products that, in specific diseases, have been found to carry mutations (e.g. the familial forms of Alzheimer's
Managing uncertainty
Methods for determining a strategy in a complex environment have received considerable attention in the management literature, but they can, in general, be divided into two approaches. One approach [29] recommends first gathering all relevant information, followed by analysis of every possible outcome of every possible decision. On the basis of this complete picture, one can then choose the optimal strategy, plan it in detail and stick to the plan until it has been implemented. This is, of
An integrated target/physiology-based drug discovery paradigm
The optimal approach to drug discovery necessarily depends upon the specific company and its strategy, but a proposal for an approach that integrates the above issues is shown in FIGURE 3, FIGURE 4. The first step is to classify the target according to the criteria in Table 1. Next, to conduct a comprehensive strategy determination that includes collecting information regarding the indication and the biology of the target; setting a clear strategy for proof-of-principle studies and determining
Conclusions
The introduction raised the question whether the shift to target-based drug discovery could be responsible for the decline in the productivity of the pharmaceutical industry. It is not the only explanation, because many factors have changed over the past 10 years [1, 2, 3, 4, 5, 6, 7, 8, 9, 10], but during this period it has been the dominating paradigm and we have seen a strong decline in the number of new molecules entering clinical testing, suggesting that it could be a contributing factor.
Acknowledgements
I thank Professor D Hinzen and Jeanette Sams-Dodd for commenting on the manuscript.
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