Drug discovery development stages

Netzer, R., Bischoff, U. and 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 Development, 6, 462—469. 

However, this conceptual apparatus does little to explain the actual way in which the public and private sectors invest in drug discovery, development and procurement. At all stages, public and private sectors inform each other in influencing the rate and direction of innovation. As argued in the introduction, markets and other institutions are co-cre-ated by public and private sectors. The discussion of VBP locates it as one example of this changing pattern of political and economic interaction and articulation, in this case in the way in which drugs are purchased and prices are determined. 

In particular, in silico methods are expected to speed up the drug discovery process, to provide a quicker and cheaper alternative to in vitro tests, and to reduce the number of compounds with unfavorable pharmacological properties at an early stage of drug development. Bad ADMET profiles are a reason for attrition of new drug candidates during the development process [9, 10]. The major reasons for attrition of new drugs are ... 

FIGURE 8.1 Schematic diagram of four interactive but separate stages of drug discovery and development. 

This chapter is written for a medicinal chemistry audience. The focus is on the importance of drug solubility in water and in dimethylsulfoxide (DMSO) in the types of activities likely to be of interest to medicinal chemists. The emphasis is on the discovery stage as opposed to the development stage. The reader will find numerous generalizations and rules of thumb relating to solubility in a drug discovery setting. 

The discovery development interface is important with respect to drug aqueous solubihty. In earlier discovery stages kinetic solubihty assays are perfectly acceptable even more desirable than the thermodynamic equilibrium solubihty assay. 

During the early stages of drug discovery, a suitable candidate must be selected from a limited number of structurally related compounds that may have a similar pharmacological profile. At that point, information from in vitro systems would provide important and particularly useful selection criteria. However, results from in vitro models are often not yet available at the early phases of development, or they exist only for a limited number of compounds. Accordingly, there is an urgent need for in silico methods that would allow prediction of the pharmacological properties in humans from the experimental model systems. 

A model for predicting oral bioavailability is an important tool, both in the early phases of drug discovery to select the most promising leads for further optimization, and in the later stages to select candidates for clinical development. The... 

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