| Abstrakt: |
The cost of bringing a new drug to market has been estimated to be close to a billion US dollars. With the recent failure of promising candidates late in the clinical trial stage and the need to add caution to the use of certain approved drugs, it has become necessary to review and critique the techniques currently used in drug discovery, including the area of computational molecular design. The theme of this guest issue is “Evolving Paradigms in Drug Design and Discovery”. Beyond the traditional approaches to drug design, newer techniques such as novel decision-making algorithms that help identify new structural candidates and identify chemical diversity metrics having biological information encoded are fast becoming an integral part of the mainstream drug discovery programs. The need for efficient data mining methods, not only at the early research stages, but also during clinical trials is paramount as the decision making processes in bringing a successful drug into market are dynamic and encompass the results of the various constituent experiments. This can prove difficult within an enterprise environment. The incorporation and use of customized automated workflows is a tool that can address such issues successfully. There has been a tendency to assume or take for granted the in-silico workhorses of Computer-Aided Drug Design - the computers that evaluate the formulas and provide the numerical results of complicated algorithms to be the successful approach. High Performance Computing has evolved over the past years in terms of processor speeds, networking and clustering configurations and the efficiency of the operating systems. It is important to review the impact of these advances in the area of molecular design. An understanding of efflux transporter mechanisms is fast becoming an area of active interest in drug design and discovery. A review on the computational modeling of the P-glycoprotein (Pgp) transporter using pharmocophoric and quantitative structureactivity relationship (QSAR) techniques within the context of optimizing the central nervous system penetration has been included. The evolving trend of introducing computational pharmacokinetic and pharmacodynamic techniques early in the drug discovery process necessitates that the available methodologies are reviewed. Commercially available software packages and applications in the area of drug discovery have been discussed in this issue. The application of techniques in the area of oncology-based drug design and discovery such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging studies in the area of tumor biology has been reviewed. Such techniques, when incorporated into a drug discovery paradigm, can reduce the time taken to discover potential liabilities in the metabolism pathways of drug candidates. In summary, it is hoped that this issue will illustrate the many aspects of various multi-disciplinary inputs that are increasingly becoming mainstream technologies in bringing a successful drug into the commercial arena. It is with this focus that this guest issue of Current Computer-Aided Drug Design reviews the areas of change in computer hardware, workflow logistics, novel methods and algorithms in drug design, together with computational pharmacokinetics and the contributions of imaging techniques in the evolving drug design, discovery and development processes. |
