Drug discovery design and serendipity

The understanding and use of medicines by physicians and healers have evolved significantly, keeping in step with technological and biological breakthroughs. From the use of herbal remedies to toxic 

the drug discovery and development process is a two-part exercise in mitigating the economic punishment to product sponsors while maximizing the probability that something that can be developed successfully is actually found. As few as 1 % of promising lead molecules will be tested in human beings fewer than one-third of those tested 

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier 2007 John Wiley Sons, Ltd ISBN 978-0-470-09313-9 

Despite the high risk and escalating costs to develop new medicines, the benefits of pharmaceuticals to human healthcare provide both financial as well as humanitarian motivation to pharmaceutical companies and to the individual drug discovery scientists. 

All drug discovery projects depend on luck to be successful, but research and careful planning can improve chances of success and lower the cost. Project teams can streamline the discovery process by using the tools that can lead to a discovery most directly. These tools are drawn from the repertoires of modem biology, chemistry, robotics and computer simulations. In comparison with older processes of in vivo screening of huge numbers of molecules, however, these innovations have not been associated with shortening of the development 

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Salemme FR, Spurlino J, Bone R. Serendipity meets precision the integration of structure-based drug design and combinatorial chemistry for efficient drug discovery. Structure 1997 5 319-324. 

F. R. Salemme, J. Spurlino, and R. Bone, Structure, S, 319 (1997). Serendipity Meets Precision The Integration of Structure-Based Drug Design and Combinatorial Chemistry for Efficient Drug Discovery. 

In conclusion, we are still in a position where the payoff from modern drug discovery techniques it still to be fully realised. However, it is my belief that when such techniques are combined with serendipity and the intuition of medicinal chemists, this represents as formidable a team as is possible. Given this as the current state of the art, the limiting obstacles to the design of new drug entities will continue to be pharmcokinetic affairs and it is in this area that a predictive black box would be most beneficial. 

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

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