Druggable target

Step 2 involves knowing what properties turn a macromolecule into a receptor. All receptors may be macromolecules, but all macromolecules are certainly not receptors. Receptor macromolecules are frequently proteins or glycoproteins. Certain properties must be present if a macromolecule is going to have what it takes to be a druggable target. The receptor macromolecule must be intimately connected with the disease in question, but not integral to the normal biochemistry of a wide range of processes. 

The evolution of methods for combinatorial syntheses and high throughput screening will be necessary to address the explosion of druggable targets soon to be identified by the genomics and proteomics revolutions. Genomics and proteomics represent the future of lead compound identification. 

Within each of these categories there is a further refinement of targets. As discussed in chapter 9, for example, possible druggable targets for antifungal drug design may be subdivided as follows ... 

Figure 7.1 Drug targets at the level of cellular structure. The mammalian cell presents a variety of druggable targets. The most important ones are located at the level of the cell membrane. Within the cell, cytoplasmic organelles, such as mitochondria, are beginning to be exploited as potential drug targets. The nucleus, at the center of the cell, is an important target for the development of antineoplastic agents for the treatment of cancer.

The cell nucleus is another important source of druggable targets. Surprisingly, the nucleus is not as important to the survival of an individual cell as are many of the cytoplasmic organelles. A cell can live without its nucleus, it just cannot reproduce. (Mature adult human red blood cells, for example, do not have nuclei.) On the other hand, a cell cannot live without its mitochondria. Therefore, the cell nucleus is an important structure to target when designing drugs for diseases in which one wishes to stop cellular reproduction (e.g., cancer, viral or bacterial infections). 

These seven groups of endogenous nonmessenger macromolecules offer a plethora of leads as both drugs and druggable targets (see figure 8.5). In a somewhat arbitrary but... 

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