Trends in Drug Discovery and Development

The approach to drug discovery and development can generally be classified into the following areas  

Irrational Approach This approach is the historical method of discovering and developing drugs. It involves empirical observations of the pharmacological effects from the screening of many chemical compounds, mainly those from natural products. The active component that gives rise to the observed effects is isolated. The chemical formula is determined, and modifications are made to improve its properties. This approach has yielded many drugs available today. 

Rational Approach This approach requires three-dimensional knowledge of the target structure involved in the disease. Drugs are designed to interact with this target structure to create a beneficial response. This is an emerging field in drug discovery started in the last 30 years. 

Antisense Approach This is a relatively new approach and it requires modifications to oligonucleotides that can bind to RNA and DNA (refer to Appendix 2 for a description of cell structure, genes, DNA, RNA, and proteins). The antisense drugs are used to stop transcriptional (from DNA) or translational (from RNA) pathways from proceeding, and so interfere with the process of disease. 

RNAi Approach This is the use of short interfering RNA (siRNA, sometimes called small interfering or silencing RNA) to interfere with the expression of a particular gene. The siRNAs are double-stranded RNAs of 20-25 nucleotides. It is envisaged that if the biological pathway of a disease is identified, siRNA could interfere to turn off the activity of the gene involved in the pathway and provide therapeutic effect. 

---

Dorman G, Prestwich GD. 2000. Using photolabile ligands in drug discovery and development. Trends Biotechnol 18 64-77. 

Netzer R, Bischoff U, Ebneth A (2003) HTS techniques to investigate the potential effects of compounds on cardiac ion channels at early-stages of drug discovery. Current Opinion in Drug Discovery and Development 6(4) 462-469 Vandenberg JI, Walker BD, Campbell TC (2001) HERG K+channels friend and foe. Trends Pharmacol Sci 22 240-246... 

There is no doubt that the combination of high-performance liquid-chromatographic (HPLC) separations with MS affords one of the most powerful, centrally applied tools in drug discovery and development [2]. While there is a clear trend toward incrementally smaller ID columns from the... 

Supercritical fluid chromatography and related teehnologies offer the opportunity for pharmaceutical companies to become more green (environmentally friendly). It remains to be see if this aspect will be embraeed or simply receive lip service. The financial incentives are very real, however, which is likely to continue the trend toward greater penetration of SEC in drug discovery and development. 

Combined with the trend of small niche companies in drug development has come the parallel corporate trend of downsizing and the hesitancy to expand divisions to take on temporary projects. A great number of large companies are contracting for critical aspects of drug discovery and development. Compounds can be manufactured xmder contract. 

There has been a revival in the use of traditional medicine (TM) in the last decade. TM is also called complementary or alternative medicine (CAM). It is likely that this revival trend will continue when there are still unmet needs to be hlled by Western drugs. The quandary with Western drugs is that pharmaceutical hrms have to ensure a reasonable return on shareholders investment. With many drug discovery and development programs costing billions of dollars, most pharmaceutical firms concentrate on blockbuster drugs with large market potential. The way is thus left open for the treatment of many diseases by other means such as TM. 

Hamon V, Crawford M, Jean T. Pharmacological and pharmaceutical profiling New trends. In O Dormell, Smith (eds), The Process of New Drug Discovery and Development, 2nd ed, Taylor and Francis/CRC Press, 2006. 

The many essential steps in the discovery and development of new drugs can be measured by two primary benchmarks. The first, the number of filed and approved investigational new drag (IND) applications, represents the threshold to human (clinical) testing. The second, the number of filed and approved new drug applications (NDAs), represents the threshold to marketing a drug. These numbers and their trends can represent the relative success of R D efforts. 

Rajamani, R. and Good, A.C. (2007) Ranking poses and structure-based lead discovery and optimization current trends in scoring function development Current Opinion in Drug Discovery ei Development, 10, 308—315. 

This chapter aims to provide chemists and biotechnologists with an overview of the state of biocatalysis and its application to different reactions in the drug discovery and development process. In Section 16.2, biocatalysts that catalyze different chemical reactions will be introduced. In Section 16.3, selected examples of mulhstep enzymatic reactions will be highlighted. Finally the chapter will be wrapped up with a discussion on current trends and future perspectives. 

---