Bottlenecks, in drug discovery

Identification of the protein target that interacts with a molecule is a bottleneck in drug discovery. Here we will deal with one branch of this important venture. 

Calvert, S., Stewart, F.P., Swarna, K. and Wiseman, J.S., The use of informatics and automation to remove bottlenecks in drug discovery Curr. Opin. Drug Discovery Develop., 1999, 2(3), 234-238. 

Beyond lead optimization, the cost savings for final marketed drug production may be dramatic if the final compound is accessible via MCR methodology, as opposed to a multi-step route. Indeed multi-step chemical process development is often a bottleneck in drug discovery. An excellent example is the HIV protease inhibitor Crixivan , which will be discussed in due course [6]. 

In order to overcome the synthesis bottleneck in drug discovery, the concept of preparing many compounds at one time (parallel synthesis) rather than one compound at a time (serial synthesis) was bom. In its simplest form, this distinction constitutes the definition of combinatorial chemistry. The origin of the concept has been ascribed (1) to Furka and others as early as 1982. Early applications of parallel synthesis methods were primarily in the area of peptide library synthesis and have been extensively reviewed (2,3). In the early 1990s, however, application to small drug-like molecules was reported (4) and the explosion in combinatorial chemistry activity began. 

In this chapter, we will present different types of biochips, including protein and antibody arrays, as well as carbohydrate, peptide and living cell arrays. We will discuss recent progress and current bottlenecks in high-throughput generation of chip content, surface chemistry, molecule attachment, detection methods, and also applications in the proteomic field and in drug discovery. 

Fig. 9 Diagrammatic representation of the different stages in drug discovery and development showing where pharmacogenomics, toxicoge-nomics, and pharmacogenetics can be applied to a more sophisticated paradigm in tandem with the use of various cell culture technologies. The different potential bottlenecks in the process are also shown.

The CSO field will not be dominated by the mega-CSOs. The present and future bottlenecks experienced by pharmaceutical companies will result in more CSOs, not fewer. These new CSOs will offer clients specialized services in drug discovery and potential for development characterization to evaluate multiple discovery leads simultaneously. 

Lead drug compound synthesis using the current knowledge of medicinal chemistry represents a significant bottleneck in the discovery chain. MW-accelerated chemistry has proved to be invaluable for the pharmaceutical industry in reducing the timescale of this process. Therefore, pharmacentical companies have invested heavily in robot-assisted MW technology. The time saving associated with the use of MW-assisted accumulation of compound libraries was... 

Combinatorial approaches make it relatively straightforward to generate chemical libraries with vast number of new compounds thus synthesis is often no longer the rate-limiting step in drug discovery. Since almost all analytical characterization tools are serial techniques, the purification and analysis of the chemical libraries has instead become a new bottleneck. This, of course, imposes new analytical challenges in the fields associated with... 

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