Discovery Process

To become familiar with the drug discovery process... 

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 ... 

Before we continue with the description of the drug discovery process, we introduce some terms commonly used in drug design and give their definitions ... 

The drug discovery process comprises the following steps ... 

Chemoinformati.cs is involved in the drug discovery process in both the lead finding and lead optimization steps. Artificial neural networks can play a decisive role of various stages in this process cf. Section 10.4.7.1). 

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Table 10.4-2. Cases m ligand structure, the drug discovery process depending on knowledge of the receptor and...

Chemoinformatics is primarily used for the steps of lead finding and lead optimization within the drug discovery process. In particular the following tasks are involved ... 

Fig. 7. The cycle of stmcmie-based dmg design. The conventional or basic cycle consists of a simple loop between chemical synthesis and biological activity. This cycle is typically initiated through a lead compound. Whereas this cycle remains the core of the dmg discovery process, the resources available...

The steps you need to take to detect specific problems will vary depending on the nature of the problem. The part that can be proceduralized is the discovery process for detecting problems and isolating their cause. A typical process may be as follows ... 

A meaningful dialogue between chemists and pharmacologists is the single most important element of the drug discovery process. The necessary link between medicinal chemistry and pharmacology has been elucidated by Paton [2] ... 

Such complex end points are difficult to predict from any one of the component processes leading to yet another leap of faith in the drug discovery process. For these reasons, an emerging strategy for drug discovery is the use of natural cellular systems. This approach is discussed in some detail in Chapter 8. 

While recombinant systems have greatly improved the drag discovery process, pathological phenotypes still are a step away from these drag testing systems. 

The cl mg discovery process can be envisioned as four interconnected phases (see Figure 8.1). Generally, these are the acquisition of chemicals to be tested for biological activity, the determination of the activity of those chemicals on biological systems (pharmacodynamics), the formulation of the most active of these for therapeutic testing in humans (pharmaceutics), and the determination of adequate delivery of the active drug to diseased tissues (pharmacokinetics). Each of these collections of processes is interconnected with the others and failure in any one of them can halt the development process. It is worth considering each process separately, as well as the relationships between them. 

A major consideration in screening is the detection capability of the screen for both false negatives (lack of detection of an active drug) and propensity to find false positives (detection of a response to the compound not due to therapeutic activity of interest). Ostensibly, false positives might not be considered a serious problem in that secondary testing will detect these and they do not normally interfere with the drug discovery process. 

The preceding discussion involves the elucidation of the primary hit and lead activity, obviously a crucial step in the drug discovery process. However, there are numerous other reasons a molecule with good primary activity may still fail... 

In general, there are three milestones for the drug discovery process. The first is the identification of a verified hit series (primary activity in a related series of molecules), the second the determination of a lead series (series with primary activity and drug-like properties), and the third a clinical candidate (activity, positive pharmaceutical, and pharmacokinetic properties devoid of toxicity). An example... 

In general, the detection of adverse drug reactions early in the drug discovery process is becoming commonplace. So-called liability panels of receptors, hERG channel activity, and cytochrome enzymes are utilized to identify... 

The drug discovery process can be divided into four subsets acquisition of chemical drug candidates, pharmacodynamic testing of large numbers of compounds (screening), and the optimization of pharmacokinetic and pharmaceutical properties. 

The ultimate model is the human in the clinical situation. Translational medicine with noninvasive imaging techniques and biomarkers is now able to furnish valuable information that can be used in the initial discovery process to produce better defined drugs. 

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